Heteroaryl substituted piperidine derivatives which are L-CPT1 inhibitors

ABSTRACT

The invention is concerned with novel substituted piperidine derivatives of formula (I) 
                         
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7  and X are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit L-CPT1 and can be used as medicaments.

PRIORITY TO RELATED APPLICATIONS

This application claims the benefit of European Application No.05111560.8, filed Dec. 1, 2005, which is hereby incorporated byreference in its entirety.

FIELD OF THE INVENTION

The invention is concerned with novel substituted piperidine derivativesof the formula (I)

and pharmaceutically acceptable salts and esters thereof.

Further, the invention is concerned with a process for the manufactureof the above compounds, pharmaceutical preparations which contain suchcompounds as well as the use of these compounds for the production ofpharmaceutical preparations.

All documents cited or relied upon below are expressly incorporatedherein by reference.

BACKGROUND

High levels of free fatty acids (FFA) lead to an increase of livermitochondrial β-oxidation, which is crucial to drive efficientgluconeogenesis. The mitochondrial oxidation of long-chain FFA requiresthe intervention of two membrane-bound carnitine-dependentpalmitoyltransferases (CPTs). CPT1, the outer mitochondrial membraneenzyme, catalyzes the formation of long-chain acylcarnitines. Liver(L-CPT1) and muscle (M-CPT1) CPT1 isoforms are encoded by two differentgenes and inhibited by malonyl-CoA. The N-ter domain of L-CPT1 confersits lower sensitivity to malonyl CoA. CPT2, the inner mitochondrialmembrane enzyme, reconverts long-chain acylcarnitines into long-chainacyl CoA esters. Long-chain acyl-CoAs are then β-oxidized to acetyl-CoA,which activates the pyruvate carboxylase and gluconeogenesis. Accordingto the mechanism of action described above, pharmaceutically activesubstances which inhibit L-CPT1 reduce liver β-oxidation, consequentlyinhibit gluconeogenesis and therefore counteract hyperglycemia.

SUMMARY OF THE INVENTION

In an embodiment of the present invention, provided is a compound offormula (I):

wherein:

-   X is C(R⁸R⁹), NR¹⁰, O, S, S(O), S(O₂);-   R¹ is phenyl optionally substituted with 1 to 3 substituents    selected from the group consisting of halogen, hydroxy, lower-alkyl,    hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-alkoxy and CN;-   R² is hydrogen or lower-alkyl;-   R³ and R⁴ independently from each other are hydrogen, halogen,    lower-alkyl or lower-alkoxy, or R³ and R⁴ together are ═O to form a    carbonyl group together with the carbon atom to which they are    attached;-   R⁵ and R⁶ independently from each other are hydrogen, halogen,    lower-alkyl or lower-alkoxy, or R⁵ and R⁶ together are ═O to form a    carbonyl group together with the carbon atom to which they are    attached;-   R⁷ is an oxadiazolyl or triazolyl, which oxadiazolyl or triazolyl is    substituted with R¹¹ and optionally substituted with R¹²;-   R⁸ and R⁹ independently from each other are hydrogen, halogen,    hydroxy, lower-alkyl, lower-alkoxy; or-   R⁸ and R⁹ are bound together and —R⁸—R⁹— is —(CH₂)₂₋₇— to form a    ring together with the carbon atom to which they are attached;-   R¹⁰ is hydrogen, lower-alkyl, lower-alkyl-carbonyl or    lower-alkyl-sulfonyl;-   R¹¹ is aryl or a heteroaryl selected from the group consisting of    pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl,    indazolyl, 1,3-dihydro-benzimidazol-2-one, 1,3-dihydro-indol-2-one,    benztriazolyl, imidazopyridinyl, triazolepyridinyl,    tetrazolepyridinyl, benzimidazolyl, 2-oxo-2,3-dihydro-1H-indol-5-yl,    pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl,    pyrimidine-2,4-dione, benzooxazin-3-one,    1,4-dihydro-benzooxazin-2-one, indolyl, thiophenyl, oxazolyl,    benzooxazin-2-one, 3,4-dihydro-quinazolin-2-one, pyridazinyl,    quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl,    cinnolinyl, 1,4-dihydro-quinoxaline-2,3-dione and    1,2-dihydro-indazol-3-one, which aryl or heteroaryl is optionally    substituted with 1 to 3 substituents selected from the group    consisting of lower-alkyl, hydroxy, B(OH)₂, carboxy-lower-alkoxy,    carbamoyl-lower-alkoxy, cyano, hydroxy-lower-alkyl,    fluoro-lower-alkyl, lower-alkoxy, halogen, S(O₂)R¹³, C(O)R¹⁴, NO₂,    NR¹⁵R¹⁶, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl,    phenyl-lower-alkoxy, [1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl    and isoxazolyl, which imidazolyl is optionally substituted with    lower-alkyl, and which phenyl-lower-alkoxy is optionally substituted    with hydroxy, halogen, lower-alkyl, lower-alkoxy or    fluoro-lower-alkyl, and which pyrazolyl is optionally substituted    with lower-alkyl, and which isoxazolyl is optionally substituted    with lower-alkyl;-   R¹² is hydrogen or lower-alkyl;-   R¹³ is lower-alkyl, NR¹⁷R¹⁸ or fluoro-lower-alkyl;-   R¹⁴ is OH, NR¹⁹R²⁰, lower-alkoxy, lower-alkenyl-oxy or lower-alkyl;-   R¹⁵ and R¹⁶ independently from each other are hydrogen, lower-alkyl,    lower-alkyl-carbonyl, lower-alkyl-SO₂, lower-alkenyl-oxy-carbonyl,    NH₂-carbonyl, lower-alkyl-NH-carbonyl, (lower-alkyl)₂N-carbonyl or    phenyl-lower-alkyl, which phenyl-lower-alkyl is optionally    substituted with hydroxy, halogen, lower-alkyl, lower-alkoxy or    fluoro-lower-alkyl; or-   NR¹⁵R¹⁶ is a heterocyclyl selected from the group consisting of    morpholinyl, thiomorpholinyl, 1,1-dioxo-thiomorpholinyl,    piperidinyl, piperidin-2-one, piperazin-2-one,    8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl, pyrrolidinyl,    1,1-dioxo-isothiazolidinyl, pyrrolidin-2-one,    imidazolidine-2,4-dione, 2,4-dihydro[1,2,4]triazol-3-one,    pyrrolidine-2,5-dione, azetidin-2-one and    1,3-dihydro-imidazol-2-one, which heterocyclyl is optionally    substituted with hydroxy-lower-alkyl or lower-alkyl-carbonyl;-   R¹⁷ and R¹⁸ independently from each other are hydrogen, lower-alkyl,    hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl; or-   NR¹⁷R¹⁸ is morpholinyl;-   R¹⁹ and R²⁰ independently from each other are hydrogen, lower-alkyl,    cycloalkyl, hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl,    (lower-alkyl)₂N-lower-alkyl, pyridinyl-lower-alkyl or    cyano-lower-alkyl; or-   NR¹⁹R²⁰ is a heterocyclyl selected from the group consisting of    morpholinyl, pyrrolidinyl, 8-oxa-3-aza-bicyclo[3.2.1]octyl,    piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl,    thiomorpholinyl, 1,3,8-triaza-spiro[4,5]decane-2,4-dione and    spiro(1-phtalan)-piperidine-4-yl, which heterocyclyl is optionally    substituted with hydroxy, lower-alkyl-S(O₂), lower-alkyl,    lower-alkyl-carbonyl, carboxy, carbamoyl, lower-alkoxy-carbonyl,    cyano, phenyl, pyridinyl or lower-alkoxy;    and pharmaceutically acceptable salts and esters thereof.

In another embodiment of the present invention, provided is a processfor the manufacture of a compound according to formula (I), comprisingthe step of reacting a compound of formula (II)

with a compound of formula (III)

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, and X are as defined in the compoundof formula (I) and L is halogen.

In a further embodiment of the present invention, provided is apharmaceutical composition, comprising a therapeutically effectiveamount of a compound according to formula (I) and a pharmaceuticallyacceptable carrier and/or adjuvant.

In a still another embodiment of the present invention, provided is amethod for the treatment of diseases which are modulated by L-CPT1inhibitors, comprising the step of administering a therapeuticallyeffective amount of a compound according to formula (I) to a human beingor animal in need thereof.

DETAILED DESCRIPTION

The present invention relates to novel compounds which inhibit livercarnitine palmitoyl transferase 1 (L-CPT1) activity. The compounds ofthe present invention can be used as pharmaceutically active agentswhich are useful in the prevention and/or treatment of diseases whichare modulated by L-CPT1 inhibitors, particularly diseases which arerelated to hyperglycemia and/or glucose tolerance disorders. Suchdiseases include e.g. diabetes and associated pathologies, non insulindependent diabetes mellitus (also referred to as diabetes type II),obesity, hypertension, insulin resistance syndrome, metabolic syndrome,hyperlipidemia, hypercholesterolemia, fatty liver disease,atherosclerosis, congestive heart failure and renal failure.

Unless otherwise indicated, the following definitions are set forth toillustrate and define the meaning and scope of the various terms used todescribe the invention herein.

In this specification the term “lower” is used to mean a groupconsisting of one to seven, preferably of one to four carbon atom(s).

The term “halogen” refers to fluorine, chlorine, bromine and iodine,with fluorine, chlorine and bromine being preferred.

The term “alkyl”, alone or in combination with other groups, refers to abranched or straight-chain monovalent saturated aliphatic hydrocarbonradical of one to twenty carbon atoms, preferably one to sixteen carbonatoms, more preferably one to ten carbon atoms. Lower-alkyl groups asdescribed below also are preferred alkyl groups.

The term “lower-alkyl”, alone or in combination with other groups,refers to a branched or straight-chain monovalent alkyl radical of oneto seven carbon atoms, preferably one to four carbon atoms. This term isfurther exemplified by such radicals as methyl, ethyl, n-propyl,isopropyl, n-butyl, s-butyl, t-butyl and the like. The term“hydroxy-lower-alkyl” refers to a lower-alkyl group which is substitutedwith hydroxy.

The term “fluoro-lower-alkyl” refers to lower-alkyl groups which aremono- or multiply substituted with fluorine. Examples offluoro-lower-alkyl groups are e.g. CFH₂, CF₂H, CF₃, CF₃CH₂, CF₃(CH₂)₂,(CF₃)₂CH and CF₂H—CF₂.

The term “alkoxy” refers to the group R′—O—, wherein R′ is an alkyl. Theterm “lower-alkoxy” refers to the group R′—O—, wherein R′ is alower-alkyl.

The term “fluoro-lower-alkoxy” refers to the group R″—O—, wherein R″ isfluoro-lower-alkyl.

Examples of fluoro-lower-alkoxy groups are e.g. CFH₂—O, CF₂H—O, CF₃—O,CF₃CH₂—O, CF₃(CH₂)₂—O, (CF₃)₂CH—O, and CF₂H—CF₂—O.

The term “alkenyl”, alone or in combination with other groups, standsfor a straight-chain or branched hydrocarbon residue comprising anolefinic bond and up to 20, preferably up to 16 carbon atoms. The term“lower-alkenyl” refers to a straight-chain or branched hydrocarbonresidue comprising an olefinic bond and up to 7, preferably up to 4carbon atoms, such as e.g. 2-propenyl.

The term “alkinyl”, alone or in combination with other groups, standsfor a straight-chain or branched hydrocarbon residue comprising a triplebond and up to 20, preferably up to 16 carbon atoms. The term“lower-alkinyl” refers to a straight-chain or branched hydrocarbonresidue comprising a triple bond and up to 7, preferably up to 4 carbonatoms, such as e.g. 2-propinyl.

The term “alkylene” refers to a straight chain or branched divalentsaturated aliphatic hydrocarbon group of 1 to 20 carbon atoms,preferably 1 to 16 carbon atoms, more preferably up to 10 carbon atoms.Lower-alkylene groups as described below also are preferred alkylenegroups.

The term “lower-alkylene” refers to a straight chain or brancheddivalent saturated aliphatic hydrocarbon group of 1 to 7, preferably 1to 6 or 3 to 6 carbon atoms. Straight chain alkylene or lower-alkylenegroups are preferred.

The term “cycloalkyl” refers to a monovalent carbocyclic radical of 3 to10 carbon atoms, preferably 3 to 6 carbon atoms, such as cyclopropyl,cyclobutyl, cyclopentyl, or cyclohexyl.

The term “aryl”, alone or in combination, relates to the phenyl ornaphthyl group, preferably the phenyl group, which can optionally besubstituted by 1 to 5, preferably 1 to 3, substituents independentlyselected from the group consisting of halogen, hydroxy, amino, NO₂,lower-alkyl, hydroxy-lower-alkyl, lower-alkoxy, carboxy,carboxy-lower-alkyl, lower-alkoxy-carbonyl,lower-alkoxy-carbonyl-lower-alkyl, lower-alkylcarbonyl,lower-alkylcarbonyloxy, lower-alkylcarbonyl-NH, H₂NC(O),(H,lower-alkyl)NC(O), (lower-alkyl)₂NC(O), H₂NC(O)-lower-alkyl,(H,lower-alkyl)NC(O)-lower-alkyl, (lower-alkyl)₂NC(O)-lower-alkyl,fluoro-lower-alkyl, fluoro-lower-alkoxy, H₂N-lower-alkyl,(H,lower-alkyl)N-lower-alkyl, (lower-alkyl)₂N-lower-alkyl,lower-alkyl-SO₂, lower-alkyl-SO₂O, lower-alkyl-SO₂—NH,lower-alkyl-SO₂—N(lower-alkyl), H₂NSO₂, (H,lower-alkyl)NSO₂,(lower-alkyl)₂NSO₂, dioxo-lower-alkylene (forming e.g. a benzodioxylgroup), cyano, heteroaryl, cycloalkyl, lower-alkoxy-lower-alkyl,lower-alkenyl, lower-alkinyl, phenyl and phenyloxy. Of the abovementioned substituents, halogen, lower-alkyl, fluoro-lower-alkyl,lower-alkoxy and fluoro-lower-alkoxy are preferred. Furthermore and morepreferably, aryl groups can be substituted as described in thedescription below.

The term “heteroaryl” refers to an aromatic 5 to 6 membered monocyclicring or 9 to 10 membered bicyclic ring which can comprise 1, 2 or 3atoms selected from nitrogen, oxygen and/or sulphur, such as furyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thienyl, isoxazolyl,oxazolyl, oxadiazolyl, imidazolyl, pyrrolyl, pyrazolyl, triazolyl,tetrazolyl, thiazolyl, isothiazolyl, 1,2,3-thiadiazolyl, benzimidazolyl,indolyl, indazolyl, benzoisothiazolyl, benzoxazolyl, benzoisoxazolyl,pyridinyl-2-one, oxadiazolyl, 1,3-dihydro-benzimidazol-2-one,1,3-dihydro-indol-2-one, benztriazolyl, imidazopyridinyl,triazolepyridinyl and tetrazolepyridinyl. Other possible heteroaryl are2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl,pyrazolyl, isoxazolyl, pyrimidine-2,4-dione, benzooxazin-3-one,1,4-dihydro-benzooxazin-2-one, indolyl, thiophenyl, oxazolyl,benzooxazin-2-one, 3,4-dihydro-quinazolin-2-one, pyridazinyl,quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl,cinnolinyl, 1,4-dihydro-quinoxaline-2,3-dione and1,2-dihydro-indazol-3-one. A heteroaryl group may optionally have asubstitution pattern as described earlier in connection with the term“aryl”. Furthermore, heteroaryl groups can preferably be substituted asdescribed in the description below.

The term “heterocyclyl” refers to 5 to 6 membered monocyclic ring or 8to 14, preferably 8 to 10, membered bi- or tricyclic ring which cancomprise 1, 2 or 3 atoms selected from nitrogen, oxygen and/or sulphur,such as morpholinyl, thiomorpholinyl, 1,1-dioxo-thiomorpholinyl,piperidinyl, piperidin-2-one, piperazin-2-one,8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl and pyrrolidinyl. Otherpossible heterocyclyl are 1,1-dioxo-isothiazolidinyl, pyrrolidin-2-one,imidazolidine-2,4-dione, 2,4-dihydro[1,2,4]triazol-3-one,pyrrolidine-2,5-dione, azetidin-2-one, 1,3-dihydro-imidazol-2-one,thiazolidinyl, 1,3,8-triaza-spiro[4,5]decane-2,4-dione andspiro(1-phtalan)-piperidine-4-yl. A heterocyclyl may optionally have asubstitution pattern as described earlier in connection with the term“aryl”. Furthermore, heterocyclyl groups can preferably be substitutedas described in the description below.

Compounds of formula (I) wherein an amino group is present can formpharmaceutically acceptable acid addition salts. Examples of suchpharmaceutically acceptable salts are salts of compounds of formula (I)with physiologically compatible mineral acids, such as hydrochloricacid, sulphuric acid, sulphurous acid or phosphoric acid; or withorganic acids, such as methanesulphonic acid, p-toluenesulphonic acid,acetic acid, lactic acid, trifluoroacetic acid, citric acid, fumaricacid, maleic acid, tartaric acid, succinic acid or salicylic acid. Theterm “pharmaceutically acceptable salts” refers to such salts. Compoundsof formula (I) in which a COOH group is present can further form saltswith bases. Examples of such salts are alkaline, earth-alkaline andammonium salts such as e.g. Na—, K—, Ca— and Trimethylammonium salt. Theterm “pharmaceutically acceptable salts” also refers to such salts.Salts obtained by the addition of an acid are preferred.

The term “pharmaceutically acceptable esters” embraces derivatives ofthe compounds of formula (I), in which a carboxy group has beenconverted to an ester. Lower-alkyl, hydroxy-lower-alkyl,lower-alkoxy-lower-alkyl, amino-lower-alkyl, mono- ordi-lower-alkyl-amino-lower-alkyl, morpholino-lower-alkyl,pyrrolidino-lower-alkyl, piperidino-lower-alkyl, piperazino-lower-alkyl,lower-alkyl-piperazino-lower-alkyl and aralkyl esters are examples ofsuitable esters. The methyl, ethyl, propyl, butyl and benzyl esters arepreferred esters. The term “pharmaceutically acceptable esters”furthermore embraces compounds of formula (I) in which hydroxy groupshave been converted to the corresponding esters with inorganic ororganic acids such as, nitric acid, sulphuric acid, phosphoric acid,citric acid, formic acid, maleic acid, acetic acid, succinic acid,tartaric acid, methanesulphonic acid, p-toluenesulphonic acid and thelike, which are non toxic to living organisms.

In detail, the present invention relates to compounds of formula (I)

wherein

-   X is C(R⁸R⁹), NR¹⁰, O, S, S(O), S(O₂);-   R¹ is phenyl optionally substituted with 1 to 3 substituents    selected from the group consisting of halogen, hydroxy, lower-alkyl,    hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-alkoxy and CN;-   R² is hydrogen or lower-alkyl;-   R³ and R⁴ independently from each other are hydrogen, halogen,    lower-alkyl or lower-alkoxy, or R³ and R⁴ together are ═O to form a    carbonyl group together with the carbon atom to which they are    attached;-   R⁵ and R⁶ independently from each other are hydrogen, halogen,    lower-alkyl or lower-alkoxy, or R⁵ and R⁶ together are ═O to form a    carbonyl group together with the carbon atom to which they are    attached;-   R⁷ is an oxadiazolyl or triazolyl, which oxadiazolyl or triazolyl is    substituted with R¹¹ and optionally substituted with R¹²;-   R⁸ and R⁹ independently from each other are hydrogen, halogen,    hydroxy, lower-alkyl, lower-alkoxy; or-   R⁸ and R⁹ are bound together and —R⁸—R⁹— is —(CH₂)₂₋₇— to form a    ring together with the carbon atom to which they are attached;-   R¹⁰ is hydrogen, lower-alkyl, lower-alkyl-carbonyl or    lower-alkyl-sulfonyl;-   R¹¹ is aryl or a heteroaryl selected from the group consisting of    pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl,    indazolyl, 1,3-dihydro-benzimidazol-2-one, 1,3-dihydro-indol-2-one,    benztriazolyl, imidazopyridinyl,    triazolepyridinyl,tetrazolepyridinyl, benzimidazolyl,    2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl,    thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidine-2,4-dione,    benzooxazin-3-one, 1,4-dihydro-benzooxazin-2-one, indolyl,    thiophenyl, oxazolyl, benzooxazin-2-one,    3,4-dihydro-quinazolin-2-one, pyridazinyl, quinoxalinyl,    benzothiazolyl, benzothiadiazolyl, naphthyridinyl, cinnolinyl,    1,4-dihydro-quinoxaline-2,3-dione and 1,2-dihydro-indazol-3-one,    which aryl or heteroaryl is optionally substituted with 1 to 3    substituents selected from the group consisting of lower-alkyl,    hydroxy, B(OH)₂, carboxy-lower-alkoxy, carbamoyl-lower-alkoxy,    cyano, hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-alkoxy,    halogen, S(O₂)R¹³, C(O)R¹⁴, NO₂, NR¹⁵R¹⁶, imidazolyl, pyrazolyl,    tetrazolyl, pyrrolyl, phenyl-lower-alkoxy, [1,3,4]oxadiazol-2-one,    oxadiazolyl, triazolyl and isoxazolyl, which imidazolyl is    optionally substituted with lower-alkyl, and which    phenyl-lower-alkoxy is optionally substituted with hydroxy, halogen,    lower-alkyl, lower-alkoxy or fluoro-lower-alkyl, and which pyrazolyl    is optionally substituted with lower-alkyl, and which isoxazolyl is    optionally substituted with lower-alkyl;-   R¹² is hydrogen or lower-alkyl;-   R¹³ is lower-alkyl, NR¹⁷R¹⁸ or fluoro-lower-alkyl;-   R¹⁴ is OH, NR¹⁹R²⁰, lower-alkoxy, lower-alkenyl-oxy or lower-alkyl;-   R¹⁵ and R¹⁶ independently from each other are hydrogen, lower-alkyl,    lower-alkyl-carbonyl, lower-alkyl-SO₂, lower-alkenyl-oxy-carbonyl,    NH₂-carbonyl, lower-alkyl-NH-carbonyl, (lower-alkyl)₂N-carbonyl or    phenyl-lower-alkyl, which phenyl-lower-alkyl is optionally    substituted with hydroxy, halogen, lower-alkyl, lower-alkoxy or    fluoro-lower-alkyl; or-   NR¹⁵R¹⁶ is a heterocyclyl selected from the group consisting of    morpholinyl, thiomorpholinyl, 1,1-dioxo-thiomorpholinyl,    piperidinyl, piperidin-2-one, piperazin-2-one,    8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl, pyrrolidinyl,    1,1-dioxo-isothiazolidinyl, pyrrolidin-2-one,    imidazolidine-2,4-dione, 2,4-dihydro[1,2,4]triazol-3-one,    pyrrolidine-2,5-dione, azetidin-2-one and    1,3-dihydro-imidazol-2-one, which heterocyclyl is optionally    substituted with hydroxy-lower-alkyl or lower-alkyl-carbonyl;-   R¹⁷ and R¹⁸ independently from each other are hydrogen, lower-alkyl,    hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl; or-   NR¹⁷R¹⁸ is morpholinyl;-   R¹⁹ and R²⁰ independently from each other are hydrogen, lower-alkyl,    cycloalkyl, hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl,    (lower-alkyl)₂N-lower-alkyl, pyridinyl-lower-alkyl or    cyano-lower-alkyl; or-   NR¹⁹R²⁰ is a heterocyclyl selected from the group consisting of    morpholinyl, pyrrolidinyl, 8-oxa-3-aza-bicyclo[3.2.1]octyl,    piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl,    thiomorpholinyl, 1,3,8-triaza-spiro[4,5]decane-2,4-dione and    spiro(1-phtalan)-piperidine-4-yl, which heterocyclyl is optionally    substituted with hydroxy, lower-alkyl-S(O₂), lower-alkyl,    lower-alkyl-carbonyl, carboxy, carbamoyl, lower-alkoxy-carbonyl,    cyano, phenyl, pyridinyl or lower-alkoxy;    and pharmaceutically acceptable salts and esters thereof.

Compounds of formula (I) are individually preferred and physiologicallyacceptable salts thereof are individually preferred and pharmaceuticallyacceptable esters thereof are individually preferred, with the compoundsof formula (I) being particularly preferred.

The compounds of formula (I) can have one or more asymmetric C atoms andcan therefore exist as an enantiomeric mixture, mixture of stereoisomersor as optically pure compounds.

Preferred compounds of formula (I) as described above are those, wherein

-   X is C(R⁸R⁹), NR¹⁰, O, S, S(O), S(O₂);-   R¹ is phenyl optionally substituted with 1 to 3 substituents    selected from the group consisting of halogen, hydroxy, lower-alkyl,    hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-alkoxy and CN;-   R² is hydrogen or lower-alkyl;-   R³ and R⁴ independently from each other are hydrogen, halogen,    lower-alkyl or lower-alkoxy, or R³ and R⁴ together are ═O to form a    carbonyl group together with the carbon atom to which they are    attached;-   R⁵ and R⁶ independently from each other are hydrogen, halogen,    lower-alkyl or lower-alkoxy, or R⁵ and R⁶ together are ═O to form a    carbonyl group together with the carbon atom to which they are    attached;-   R⁷ is an oxadiazolyl or triazolyl, which oxadiazolyl or triazolyl is    substituted with R¹¹ and optionally substituted with R¹²;-   R⁸ and R⁹ independently from each other are hydrogen, halogen,    hydroxy, lower-alkyl, lower-alkoxy; or-   R⁸ and R⁹ are bound together and —R⁸—R⁹— is —(CH₂)₂₋₇— to form a    ring together with the carbon atom to which they are attached;-   R¹⁰ is hydrogen, lower-alkyl, lower-alkyl-carbonyl or    lower-alkyl-sulfonyl;-   R¹¹ is aryl or a heteroaryl selected from the group consisting of    pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl,    indazolyl, 1,3-dihydro-benzimidazol-2-one, 1,3-dihydro-indol-2-one,    benztriazolyl, imidazopyridinyl,    triazolepyridinyl,tetrazolepyridinyl and benzimidazolyl, which aryl    or heteroaryl is optionally substituted with 1 to 3 substituents    selected from the group consisting of lower-alkyl,    hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-alkoxy, halogen,    S(O₂)R¹³, C(O)R¹⁴, NO₂, NR¹⁵R¹⁶, imidazolyl, pyrazolyl, tetrazolyl,    pyrrolyl, and phenyl-lower-alkoxy, which imidazolyl is optionally    substituted with lower-alkyl and which phenyl-lower-alkoxy is    optionally substituted with hydroxy, halogen, lower-alkyl,    lower-alkoxy or fluoro-lower-alkyl;-   R¹² is hydrogen or lower-alkyl;-   R¹³ is lower-alkyl, NR¹⁷R¹⁸ or fluoro-lower-alkyl;-   R¹⁴ is OH, NR¹⁹R²⁰, lower-alkoxy or lower-alkenyl-oxy;-   R¹⁵ and R¹⁶ independently from each other are hydrogen, lower-alkyl,    lower-alkyl-carbonyl, lower-alkyl-SO₂, lower-alkenyl-oxy-carbonyl,    NH₂-carbonyl, lower-alkyl-NH-carbonyl, (lower-alkyl)₂N-carbonyl or    phenyl-lower-alkyl, which phenyl-lower-alkyl is optionally    substituted with hydroxy, halogen, lower-alkyl, lower-alkoxy or    fluoro-lower-alkyl; or-   NR¹⁵R¹⁶ is a heterocyclyl selected from the group consisting of    morpholinyl, thiomorpholinyl, 1,1-dioxo-thiomorpholinyl,    piperidinyl, piperidin-2-one, piperazin-2-one,    8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl and pyrrolidinyl, which    heterocyclyl is optionally substituted with hydroxy-lower-alkyl or    lower-alkyl-carbonyl;-   R¹⁷ and R¹⁸ independently from each other are hydrogen, lower-alkyl,    hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl; or-   NR¹⁷R¹⁸ is morpholinyl;-   R¹⁹ and R²⁰ independently from each other are hydrogen, lower-alkyl,    cycloalkyl, hydroxy-lower-alkyl or lower-alkoxy-lower-alkyl; or-   NR¹⁹R²⁰ is a heterocyclyl selected from the group consisting of    morpholinyl, pyrrolidinyl and 8-oxa-3-aza-bicyclo[3.2.1]octyl, which    heterocyclyl is optionally substituted with hydroxy or    lower-alkyl-S(O₂);    and pharmaceutically acceptable salts and esters thereof.

Preferred compounds of formula (I) as described above are those, whereinR¹ is phenyl optionally substituted with halogen, hydroxy,hydroxy-lower-alkyl or CN, more preferably those wherein R¹ is phenyl.

Other preferred compounds are those, wherein R² is hydrogen. Furtherpreferred compounds are those, wherein R³ is hydrogen. Still otherpreferred compounds are those, wherein R⁴ is hydrogen. Other preferredcompounds are those, wherein R⁵ is hydrogen. Compounds wherein R⁶ ishydrogen are alo preferred.

Preferably, R⁷ which are an oxadiazolyl are not substituted with R¹². Ina preferred embodiment of the present invention, R⁷ is

wherein R¹¹ and R¹² are as defined above. Preferably, R⁷ is

wherein R¹¹ and R¹² are as defined in claim 1.

Furthermore, it is preferred that R⁷ is

wherein R¹¹ is as defined above.

Preferred compounds of formula (I) as described above are those, whereinX is C(R⁸R⁹), NR¹⁰, O or S, wherein R⁸, R⁹ and R¹⁰ are as defined above.Preferably, X is C(R⁸R⁹) or NR¹⁰, wherein R⁸, R⁹ and R¹⁰ are as definedabove.

In the compounds as defined above, it is preferred that R⁸ is hydrogen.Preferably, R⁹ is hydrogen. It is also preferred, that R¹⁰ is hydrogen.

Another preferred embodiment of the present invention refers tocompounds as defined above, wherein R¹¹ is phenyl or a heteroarylselected from the group consisting of pyridinyl, pyrazinyl,pyridinyl-2-one, indazolyl, 1,3-dihydro-benzimidazol-2-one,1,3-dihydro-indol-2-one, benztriazolyl and benzimidazolyl, which phenylor heteroaryl is optionally substituted with 1 to 2 substituentsselected from the group consisting of lower-alkyl, hydroxy-lower-alkyl,fluoro-lower-alkyl, lower-alkoxy, halogen, S(O₂)R¹³, C(O)R¹⁴, NO₂,NR¹⁵R¹⁶, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, andphenyl-lower-alkoxy, which imidazolyl is optionally substituted withlower-alkyl, wherein R¹³, R¹⁴, R¹⁵ and R¹⁶ are as defined above.

Preferably, R¹¹ is phenyl or a heteroaryl selected from the groupconsisting of pyridinyl, pyridinyl-2-one, indazolyl,1,3-dihydro-benzimidazol-2-one, 1,3-dihydro-indol-2-one, benztriazolyland benzimidazolyl, which phenyl or heteroaryl is optionally substitutedwith 1 to 2 substituents selected from the group consisting offluoro-lower-alkyl, halogen, C(O)R¹⁴ and NR¹⁵R¹⁶, wherein R¹⁴, R¹⁵ andR¹⁶ are as defined above.

More preferably, R¹¹ is 1H-Indazol-5-yl, 1H-Indazol-6-yl,1,3-dihydro-indol-2-one-6-yl, 1,3-dihydro-benzoimidazol-2-one-5-yl,1,3-dihydro-indol-2-one-5-yl, 1H-Benzotriazol-5-yl,1H-Benzoimidazol-5-yl, 1H-pyridin-2-one-4-yl, 4-Fluoro-phenyl,3-trifluoromethyl-phenyl, 1H-Benzoimidazol-5-yl, 3-benzamide,5-nicotinamide, 3-(N-acetamide)-phenyl or3-(N-methanesulfonamide)-phenyl.

Another preferred embodiment of the present invention refers tocompounds as defined above, wherein R¹¹ is phenyl or a heteroarylselected from the group consisting of 2-oxo-2,3-dihydro-1H-indol-5-yl,pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl,pyrimidine-2,4-dione, benzooxazin-3-one, 1,4-dihydro-benzooxazin-2-one,indolyl, thiophenyl, oxazolyl, benzooxazin-2-one,3,4-dihydro-quinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl,benzothiadiazolyl, naphthyridinyl, cinnolinyl,1,4-dihydro-quinoxaline-2,3-dione and 1,2-dihydro-indazol-3-one, whichphenyl or heteroaryl is optionally substituted with 1 to 3 substituentsselected from the group consisting of hydroxy, B(OH)₂,carboxy-lower-alkoxy, carbamoyl-lower-alkoxy, cyano,[1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, whichpyrazolyl is optionally substituted with lower-alkyl, and whichisoxazolyl is optionally substituted with lower-alkyl.

Preferably, R¹¹ is phenyl or a heteroaryl selected from the groupconsisting of pyridinyl, 1,3-dihydro-indol-2-one, 1H-benzimidazolyl,3H-pyrimidin-4-one, 1H-pyrazolyl, isoxazolyl and4H-benzo[1,4]oxazin-3-one, which phenyl or heteroaryl is optionallysubstituted with 1 to 3 substituents selected from the group consistingof lower-alkyl, hydroxy, halogen and NR¹⁵R¹⁶, wherein R¹⁴ and R¹⁵ are asdefined in claim 1.

More preferably, R¹¹ is 2-methyl-3H-pyrimidin-4-one,5-methyl-isoxazol-3-yl, 1H-pyrazol-3-yl, 6-amino-pyridin-3-yl,1,3-dihydro-indol-2-one, 2-amino-pyridin-4-yl,4H-benzo[1,4]oxazin-3-one, 1H-benzimidazol-5-yl,3-(N-acetamide)-4-fluoro-phenyl or 2-hydroxy-pyridin-4-yl.

Preferably, R¹² is hydrogen. Compounds as defined above, wherein R¹³ islower-alkyl are also preferred. Other preferred compounds are those,wherein R¹⁴ is NR¹⁹R²⁰, wherein R¹⁹ and R²⁰ are as defined above. Otherpreferred compounds are those, wherein R¹⁴ is lower-alkyl.

Another preferred embodiment of the present invention refers tocompounds as defined above, wherein R¹⁵ and R¹⁶ independently from eachother are hydrogen, lower-alkyl, lower-alkyl-carbonyl, lower-alkyl-SO₂,lower-alkenyl-oxy-carbonyl or lower-alkyl-NH-carbonyl; or NR¹⁵R¹⁶ is aheterocyclyl selected from the group consisting of morpholinyl,thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, piperidinyl,piperidin-2-one, piperazin-2-one, piperazinyl and pyrrolidinyl, whichheterocyclyl is optionally substituted with hydroxy-lower-alkyl orlower-alkyl-carbonyl. More preferably, R¹⁵ and R¹⁶ independently fromeach other are hydrogen, lower-alkyl-carbonyl or lower-alkyl-SO₂.

Other preferred compounds are those, wherein NR¹⁵R¹⁶ is a heterocyclylselected from the group consisting of 1,1-dioxo-isothiazolidinyl,pyrrolidin-2-one, imidazolidine-2,4-dione,2,4-dihydro[1,2,4]triazol-3-one, pyrrolidine-2,5-dione, azetidin-2-oneand 1,3-dihydro-imidazol-2-one, which heterocyclyl is optionallysubstituted with hydroxy-lower-alkyl or lower-alkyl-carbonyl.

Other preferred compounds are those, wherein R¹⁷ and R¹⁸ independentlyfrom each other are hydrogen or lower-alkyl; or NR¹⁷R¹⁸ is morpholinyl.

Further preferred compounds as defined above are those, wherein R¹⁹ andR²⁰ independently from each other are hydrogen, lower-alkyl, cycloalkyl,hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl; or NR¹⁹R²⁰ is aheterocyclyl selected from the group consisting of morpholinyl orpyrrolidinyl, which heterocyclyl is optionally substituted with hydroxyor lower-alkyl-S(O₂). More preferably, R¹⁹ and R²⁰ are hydrogen.

Other preferred compounds are those, wherein R¹⁹ and R²⁰ independentlyfrom each other are (lower-alkyl)₂N-lower-alkyl, pyridinyl-lower-alkylor cyano-lower-alkyl; or NR¹⁹R²⁰ is a heterocyclyl selected from thegroup consisting of piperidinyl, piperazinyl, piperazin-2-one,thiazolidinyl, thiomorpholinyl, 1,3,8-triaza-spiro[4,5]decane-2,4-dioneand spiro(1-phtalan)-piperidine-4-yl, which heterocyclyl is optionallysubstituted with hydroxy, lower-alkyl-S(O₂), lower-alkyl,lower-alkyl-carbonyl, carboxy, carbamoyl, lower-alkoxy-carbonyl, cyano,phenyl, pyridinyl or lower-alkoxy.

Preferred compounds of formula (I) as defined above are those, which areR-isomers and which are characterised by formula (Ia)

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and X are as defined above.

In particular, preferred compounds are the compounds of formula (I)described in the examples as individual compounds as well aspharmaceutically acceptable salts as well as pharmaceutically acceptableesters thereof.

Preferred compounds of formula (I) are those selected from the groupconsisting of:

-   (R)-1-{2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-3-(2-{2-[3-(4-Methoxy-phenyl)[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-oxo-ethoxy)    benzonitrile,-   (R)    1-{2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-propan-1-one,-   (R)-1-{2-[3-(4-Bromo-phenyl)[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-2-(4-Hydroxy-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-2-(4-Chloro-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-2-(4-Hydroxymethyl-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-2-(3-Chloro-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-2-(4-Fluoro-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-1-{2-[3-(4-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Methane-sulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   (R)-2-(4-Fluoro-phenoxy)-1-[2-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-ethanone,-   (R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid methyl ester,-   (R)-1-{2-[3-(3-Nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   (R)-2-Phenoxy-1-[2-(3-pyrazin-2-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-ethanone,-   (R)-1-(2-{3-[4-(Morpholine-4-sulfonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-1-{2-[3-(6-Methoxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(3-Hydroxymethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinic    acid allyl ester,-   (R)-1-{2-[3-(4-Imidazol-1-yl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-N-Methyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   (R)-1-{2-[3-(6-Morpholin-4-yl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-2-Phenoxy-1-{2-[3-(4-trifluoromethanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-2-Phenoxy-1-{2-[3-(4-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-1-{2-[3-(4-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-N-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-2-trifluoromethyl-phenyl)-acetamide,-   (R)-1-{2-[3-(3-Methanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Methyl-3-nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Methoxy-3-nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-N-(2-Hydroxy-ethyl)-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   (R)-N-(2-Methoxy-ethyl)-N-methyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   (R)-N,N-Dimethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   (R)-N,N-Diethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   (R)-1-{2-[3-(2-Morpholin-4-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-2-Phenoxy-1-{2-[3-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4′-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-2-Phenoxy-1-{2-[3-(2-thiomorpholin-4-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-1-{2-[3-(2-Diethylamino-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid ethyl ester,-   (R)-1-(2-{3-[6-(4-Acetyl-piperazin-1-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-1-{2-[3-(2-Imidazol-1-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-piperidin-2-one,-   (R)-1-(2-{3-[4-(3H-Imidazol-4-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-1-(2-{3-[4-(2-Methyl-imidazol-1-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-2-Phenoxy-1-{2-[3-(2-pyrazol-1-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   (R)-4-(5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridin-2-yl)-piperazin-2-one,-   (R)-2-Phenoxy-1-(2-{3-[4-(1H-tetrazol-5-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-ethanone,-   (R)-1-{2-[3-(1H-Indazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(1H-Indazol-6-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Fluoro-3-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-benzoimidazol-2-one,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,-   (R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-(2-{3-[6-(1,1-Dioxo-thiomorpholin-4-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-N-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridin-2-yl)-acetamide,-   (R)-1-{2-[3-(6-Benzyloxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinic    acid ethyl ester,-   (R)-4-{5-[4-(2-Phenoxy-acetyl)-morpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridin-2-one,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridin-2-one,-   (R)-2-Phenoxy-1-[2-(5-phenyl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,-   (R)-1-{2-[5-(4-Methanesulfonyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[5-(3,4-Dimethoxy-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[5-(3,4-Dichloro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxyethanone,-   (R)-1-{2-[5-(4-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-2-Phenoxy-1-{2-[5-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-ethanone,-   (R)-1-{2-[5-(4-Methoxy-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[5-(3-Nitro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoic    acid methyl ester,-   (R)-1-{2-[5-(4-Fluoro-3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,3-dihydro-indol-2-one,-   1-{3-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-morpholin-4-yl}-2-phenoxy-ethanone,-   1-{3-[3-(4-Methanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-morpholin-4-yl}-2-phenoxy-ethanone,-   4-{5-[4-(2-Phenoxy-acetyl)-morpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   1-(3-{3-[6-(1,1-Dioxo-thiomorpholin-4-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-morpholin-4-yl)-2-phenoxy-ethanone,-   N-(4-{5-[4-(2-Phenoxy-acetyl)-morpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-pyridin-2-yl)-acetamide,-   1-{3-[5-(4-Methanesulfonyl-phenyl)-2H-[1,2,4]triazol-3-yl]-morpholin-4-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-{3-[5-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-morpholin-4-yl}-ethanone,-   (R)-4-{5-[4-(2-Phenoxy-acetyl)-morpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridin-2-one,-   1-{3-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-thiomorpholin-4-yl}-2-phenoxy-ethanone,-   1-{3-[3-(4-Methanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-thiomorpholin-4-yl}-2-phenoxy-ethanone,-   4-{5-[4-(2-Phenoxy-acetyl)-thiomorpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   2-Phenoxy-1-[3-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)-thiomorpholin-4-yl]-ethanone,-   1-{2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   N-(5-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridin-2-yl)-acetamide,-   1-{2-[3-(2-Imidazol-1-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   N,N-Diethyl-4-{5-[1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   N,N-Dimethyl-4-{5-[1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   4-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   1-{2-[3-(4-Methanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-[2-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)-piperazin-1-yl]-ethanone,-   1-{2-[3-(2,4-Dichloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-[2-(3-pyridin-2-yl-[1,2,4]oxadiazol-5-yl)-piperazin-1-yl]-ethanone,-   2-Phenoxy-1-[2-(3-pyridin-2-yl-[1,2,4]oxadiazol-5-yl)-piperazin-2-yl]-ethanone,-   1-{2-[3-(4-Nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[3-(6-Methoxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[3-(6-Morpholin-4-yl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[3-(6-Morpholin-4-yl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[3-(3-Hydroxymethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[3-(4-Diethylamino-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-(2-{3-[4-(Morpholine-4-sulfonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone,-   N-Methyl-4-{5-[1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   N-(2-Methoxy-ethyl)-N-methyl-4-{5-[1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   1-{2-[3-(4-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   N-(4-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-2-trifluoromethyl-phenyl)-acetamide,-   4-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid allyl ester,-   1-{2-[3-(4-Methyl-3-nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[3-(4-Methoxy-3-nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[3-(4-Chloro-3-nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   3-Fluoro-4-{5-[1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid methyl ester,-   4-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid ethyl ester,-   2-Phenoxy-1-{2-[3-(4-piperidin-1-yl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-ethanone,-   1-{2-[3-(4-Morpholin-4-yl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-(2-{3-[4-(2-Methyl-imidazol-1-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone,-   1-(2-{3-[4-(3H-Imidazol-4-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone,-   4-(5-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridin-2-yl)-piperazin-2-one,-   1-{2-[3-(6-Imidazol-1-yl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-(2-{3-[6-(4-Acetyl-piperazin-1-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone,-   2-Phenoxy-1-{2-[3-(4-pyrrol-1-yl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-ethanone,-   2-Phenoxy-1-{2-[3-(4-trifluoromethanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-ethanone,-   1-{2-[3-(2-Morpholin-4-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-{2-[3-(2-thiomorpholin-4-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-ethanone,-   1-(2-{3-[6-(3-Hydroxymethyl-pyrrolidin-1-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone,-   (R)-1-{2-[3-(6-Methoxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(6-Morpholin-4-yl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-N-(4-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-2-trifluoromethyl-phenyl)-acetamide,-   (R)-1-{2-[3-(4-Methyl-3-nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Methyl-3-nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Morpholin-4-yl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-(2-{3-[4-(3H-Imidazol-4-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone,-   (R)-1-(2-{3-[6-(3-Hydroxymethyl-pyrrolidin-1-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone,-   (R)-1-(2-{3-[6-(4-Acetyl-piperazin-1-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone,-   (R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide    hydrochloride,-   (R)-1-{2-[3-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(1H-Indazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone    hydrochloride,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-benzoimidazol-2-one,-   (R)-1-(2-{3-[6-(1,1-Dioxo-thiomorpholin-4-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone    hydrochloride,-   (R)-1-{2-[3-(3-Nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridin-2-one,-   1-{4-Acetyl-2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{4-Acetyl-2-[3-(4-methanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   4-{5-[4-Acetyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,-   1-[4-Acetyl-2-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)-piperazin-1-yl]-2-phenoxy-ethanone,-   1-{4-Methanesulfonyl-2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[5-(4-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-2-Phenoxy-1-{2-[5-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-ethanone,-   1-{2-[5-(4-Fluoro-3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[5-(4-Methanesulfonyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-{2-[5-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-ethanone,-   2-Phenoxy-1-[2-(5-p-tolyl-2H-[1,2,4]triazol-3-yl)-piperazin-1-yl]-ethanone,-   2-Phenoxy-1-{2-[5-(4-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-ethanone,-   1-{2-[5-(4-Methoxy-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[5-(4-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[5-(4-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[5-(3,4-Dimethoxy-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[5-(3,4-Dichloro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[5-(2-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   1-{2-[5-(2-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   4-{5-[4-Methyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-1-{2-[3-(1H-Indazol-5yl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-5-{5-[4-Methyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,-   (R)-5-{5-[4-Methyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-benzoimidazol-2-one,-   (R)-1-{2-[3-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{4-Methyl-2-[5-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[5-(4-Methoxy-phenyl)-2H-[1,2,4]triazol-3-yl]-4-methyl-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[5-(4-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4-methyl-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[5-(4-Methanesulfonyl-phenyl)-2H-[1,2,4]triazol-3-yl]-4-methyl-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-4-{5-[4-Methyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoic    acid methyl ester,-   (R)-N-(3-{5-[4-Methyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-1    H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,-   (R)-N-(3-{5-[4-Methyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-methanesulfonamide,-   (R)-4-{5-[4-Methyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid,-   (R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid,-   (R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinic    acid,-   (R)-2-Fluoro-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid,-   (R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoic    acid,-   3-{5-[4-(2-Phenoxy-acetyl)-morpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid,-   3-{5-[4-(2-Phenoxy-acetyl)-morpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid,-   4-{5-[4-(2-Phenoxy-acetyl)-thiomorpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   4-{5-[4-(2-Phenoxy-acetyl)-thiomorpholin-3-yl]-[1,2,4]oxadiazol-4-yl}-benzamide,-   3-{5-[4-Acetyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid,-   4-{5-[4-Acetyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic    acid,-   (R)-4-{5-[4-Methyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoic    acid,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinic    acid,-   1-(2-{3-[4-(Morpholine-4-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-1-(2-{3-[4-(3-Hydroxy-pyrrolidine-1-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-N,N-Diethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-Methyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N,N-Dimethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-Ethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-Cyclopropyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-(2-Hydroxy-ethyl)-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-(2-Methoxy-ethyl)-N-methyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-Methyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N,N-Dimethyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-Ethyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-Cyclopropyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-(2-Hydroxy-ethyl)-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-(2-Methoxy-ethyl)-N-methyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-1-(2-{3-[3-(Morpholine-4-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-1-(2-{3-[3-(3-Hydroxy-pyrrolidine-1-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-N,N-Diethyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid methylamide,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid dimethylamide,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid ethylamide,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid diethylamide,-   (R)-1-(2-{3-[2-(Morpholine-4-carbonyl)-pyridin-4-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-1-(2-{3-[2-(3-Methanesulfonyl-pyrrolidine-1-carbonyl)-pyridin-4-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid methylamide,-   (R)-N-Methyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,-   1N,N-Diethyl-4-{5-[1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   1-(2-{3-[4-(Morpholine-4-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperazin-1-yl)-2-phenoxy-ethanone,-   N-Methyl-4-{5-[1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-N-Methyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,-   (R)-N-Ethyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,-   (R)-N-Diethyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,-   (R)-N-Diethyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,-   (R)-N-(2-Hydroxy-ethyl)-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,-   (R)-N-(2-Methoxy-ethyl)-N-methyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl][1,2,4]oxadiazol-3-yl}-nicotinamide,-   (R)-N-Cyclopropyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,-   (R)-1-(2-{3-[5-(3-Hydroxy-pyrrolidine-1-carbonyl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   (R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylic    acid amide,-   (R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,-   4-{5-[4-(2-Phenoxy-acetyl)-morpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   4-{5-[4-(2-Phenoxy-acetyl)-thiomorpholin-3yl]-[1,2,4]oxadiazol-3yl}-benzamide,-   4-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,-   (R)-1-{2-[3-(3-Amino-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(4-Amino-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[5-(3-Amino-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide,-   (R)-N-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide,-   (R)-N-(5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridin-2-yl)-acetamide,-   (R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,-   (R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-methanesulfonamide,-   (R)-N-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-methanesulfonamide,-   (R)-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-carbamic    acid allyl ester,-   (R)-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-carbamic    acid allyl ester,-   (R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-methanesulfonamide,-   (R)-1-Ethyl-3-(3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-urea,-   (R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzonitrile,    and-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinonitrile,    and pharmaceutically acceptable salts and esters thereof.

Particularly preferred compounds of formula (I) are those selected fromthe group consisting of:

-   (R)-1-{2-[3-(1H-Indazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(1H-Indazol-6-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-benzoimidazol-2-one,-   (R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,-   (R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-1-{2-[3-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-4-{5-[4-(2-Phenoxy-acetyl)-morpholin-3-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridin-2-one,-   (R)-1-{2-[5-(4-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   (R)-2-Phenoxy-1-{2-[5-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-ethanone,-   (R)-1-{2-[3-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,-   5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,-   (R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,    and-   (R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-methanesulfonamide,    and pharmaceutically acceptable salts and esters thereof.

Other preferred compounds of formula (I) are those selected from thegroup consisting of:

-   1-{(R)-2-[3-(2-Methyl-1H-benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[3-(2-Amino-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[3-(3-Hydroxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   4-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridin-2-one,-   1-{(R)-2-[3-(4-Hydroxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenylboronic    acid,-   4-(2-Oxo-2-{(R)-2-[3-(2-oxo-2,3-dihydro-1H-indol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethoxy)-benzonitrile,-   4-(2-{(R)-2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-oxo-ethoxy)-benzonitrile,-   2-Methyl-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-3H-pyrimidin-4-one,-   1-[(R)-2-(3-Furan-2-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-2-phenoxy-ethanone,-   1-[(R)-2-(3-Imidazo[1,2-a]pyridin-2-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-2-phenoxy-ethanone,-   1-{(R)-2-[3-(4-Methyl-[1,2,3]thiadiazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[3-(2,5-Dimethyl-2H-pyrazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-{(R)-2-[3-(1H-pyrazol-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   1-{(R)-2-[3-(5-Methyl-isoxazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-{(R)-2-[3-(1H-pyrazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyrimidine-2,4-dione,-   1-{(R)-2-[3-(6-Amino-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-[(R)-2-(3-Imidazo[1,2-a]pyridin-6-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-2-phenoxy-ethanone,-   6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-4H-benzo[1,4]oxazin-3-one,-   6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,4-dihydro-benzo[d][1,3]oxazin-2-one,-   1-((R)-2-{3-[3-(1,1-Dioxo-1λ6-isothiazolidin-2-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-pyrrolidin-2-one,-   1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-imidazolidine-2,4-dione,-   4-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one,-   1-(3-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-pyrrolidine-2,5-dione,-   5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,3-dihydro-indol-2-one,-   1-{(R)-2-[5-(1H-Indazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(1H-Indol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(3H-Benzotriazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,3-dihydro-benzoimidazol-2-one,-   1-{(R)-2-[5-(2-Methyl-1H-benzoimidazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(2-Amino-pyridin-4-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   5-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-3H-[1,3,4]oxadiazol-2-one,-   1-{(R)-2-[5-(3-[1,3,4]Oxadiazol-2-yl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenylboronic    acid,-   6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-4H-benzo[1,4]oxazin-3-one,-   1-[(R)-2-(5-Imidazo[1,2-a]pyridin-6-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,-   1-{(R)-2-[5-(6-Amino-pyridin-3-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(1H-Benzoimidazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-[(R)-2-(5-pyridin-3-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,-   1-{(R)-2-[5-(3,5-Dimethyl-isoxazol-4-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-[(R)-2-(5-thiophen-2-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,-   2-Phenoxy-1-[(R)-2-(5-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,-   1-{(R)-2-[5-(4-Methyl-oxazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-[(R)-2-(5-pyrazin-2-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,-   1-{(R)-2-[5-(2-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(3,5-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(2-Methyl-pyridin-4-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(3-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(3,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,4-dihydro-benzo[d][1,3]oxazin-2-one,-   7-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-3,4-dihydro-1H-quinazolin-2-one,-   1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-imidazolidine-2,4-dione,-   1-{(R)-3-[3-(2-Amino-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-morpholin-4-yl}-2-phenoxy-ethanone,-   1-{(R)-3-[3-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-morpholin-4-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[3-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,-   1-{(R)-2-[3-(2-Amino-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-2-phenoxy-ethanone,-   (3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenoxy)-acetic    acid,-   2-Phenoxy-1-((R)-2-{5-[3-(piperidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-ethanone,-   1-((R)-2-{5-[3-(Morpholine-4-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   1-((R)-2-{5-[3-(4-Methyl-piperazine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   4-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-piperazin-2one,-   N-(2-Methoxy-ethyl)-N-methyl-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,-   1-((R)-2-{5-[3-(4-Acetyl-piperazine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-piperidine-4-carboxylic    acid,-   1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-piperidine-4-carboxylic    acid amide,-   2-Phenoxy-1-((R)-2-{5-[3-(thiazolidine-3-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-ethanone,-   N-(2-Dimethylamino-ethyl)-N-methyl-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,-   2-Phenoxy-1-((R)-2-{5-[3-(thiomorpholine-4-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-ethanone,-   4-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-piperazine-1-carboxylic    acid ethyl ester,-   N-(2-Hydroxy-ethyl)-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,-   N-Methyl-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-N-(2-pyridin-2-yl-ethyl)-benzamide,-   N-(2-Cyano-ethyl)-N-cyclopropyl-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,-   1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-4-phenyl-piperidine-4-carbonitrile,-   1-((R)-2-{5-[3-(4-Hydroxy-piperidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   8-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-1,3,8-triaza-spiro[4.5]decane-2,4-dione,-   1-(2-{5-[3-(Spiro(1-Phtalan)-piperidine-4-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   2-Phenoxy-1-((R)-2-{5-[3-(3-pyridin-4-yl-pyrrolidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-ethanone,-   1-((R)-2-{5-[3-(3-Methanesulfonyl-pyrrolidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   1-((R)-2-{5-[3-((S)-3-Ethoxy-pyrrolidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   1-((R)-2-{5-[3-((S)-3-Hydroxy-pyrrolidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-nicotinamide,-   2-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenoxy)-acetamide,-   N-(3-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide,-   N-(2-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide,-   N-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-propionamide,-   N-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-isobutyramide,-   N-(4-Fluoro-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,-   N-(3-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,-   N-(2-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,-   N-(4-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-pyridin-2-yl)-acetamide,-   1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-azetidin-2-one,-   1-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-pyrrolidine-2,5-dione,-   2-Phenoxy-1-[(R)-2-(5-pyridazin-4-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-ethanone,-   4-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-benzonitrile,-   1-{(R)-2-[5-(3-Amino-pyrazin-2-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-benzonitrile,-   1-{(R)-2-[5-(2-Hydroxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(5-Amino-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(2-Hydroxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(2-Hydroxy-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(4-Hydroxy-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(2-Amino-5-chloro-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-[(R)-2-(5-pyrazin-2-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-ethanone,-   2-Phenoxy-1-{(R)-2-[5-(4-[1,2,4]triazol-1-yl-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,-   2-Phenoxy-1-{(R)-2-[5-(4-tetrazol-1-yl-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,-   1-{(R)-2-[5-(1H-Benzoimidazol-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(4-Acetyl-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(6-Hydroxy-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(5-Methyl-pyrazin-2-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-[(R)-2-(5-quinoxalin-2-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-ethanone,-   1-{(R)-2-[5-(3-Methanesulfonyl-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(6-Chloro-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-[(R)-2-(5-Benzothiazol-6-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,-   2-Phenoxy-1-{(R)-2-[5-(2,4,5-trifluoro-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,-   2-Phenoxy-1-{(R)-2-[5-(6-trifluoromethyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,-   1-[(R)-2-(5-Benzo[1,2,3]thiadiazol-5-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,-   1-[(R)-2-(5-[1,8]Naphthyridin-2-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,-   1-[(R)-2-(5-[1,6]Naphthyridin-2-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,-   1-[(R)-2-(5-Cinnolin-4-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,-   1-{(R)-2-[5-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(3,6-Dichloro-pyridazin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   6-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-4H-benzo[1,4]oxazin-3-one,-   1-{(R)-2-[5-(3H-Imidazo[4,5-b]pyridin-6-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   N-(4-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-pyridin-2-yl)-acetamide,-   1-{(R)-2-[5-(6-Chloro-3-hydroxy-pyridazin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   6-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-1,4-dihydro-quinoxaline-2,3-dione,-   1-{(R)-2-[5-(6-Hydroxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   7-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-3,4-dihydro-1H-quinoxalin-2-one,-   1-{(R)-2-[5-(6-Amino-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   6-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-nicotinonitrile,-   5-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-pyridine-2-carbonitrile,-   4-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-1,2-dihydro-indazol-3-one,-   1-{(R)-2-[5-(2-Amino-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(6-Hydroxy-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   4-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one,-   1-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-imidazolidine-2,4-dione,-   1-((R)-2-{5-[3-(1,1-Dioxo-1λ6-isothiazolidin-2-yl)-phenyl]-[1,2,4]oxadiazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,-   1-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-pyrrolidin-2-one,-   1-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-1,3-dihydro-imidazol-2-one,-   3-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-imidazolidine-2,4-dione,-   1-{(R)-2-[5-(1-Methyl-1H-pyrazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-{(R)-2-[5-(1H-pyrazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,-   1-{(R)-2-[5-(5-Methyl-isoxazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(2,5-Dimethyl-2H-pyrazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(5-Methyl-2H-pyrazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,    and-   1-{(R)-2-[5-(3-Methyl-isoxazol-5-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,    and pharmaceutically acceptable salts and esters thereof.

Other particularly preferred compounds of formula (I) are those selectedfrom the group consisting of:

-   2-Methyl-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-3H-pyrimidin-4-one,-   1-{(R)-2-[3-(5-Methyl-isoxazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   2-Phenoxy-1-{(R)-2-[3-(1H-pyrazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,-   1-{(R)-2-[3-(6-Amino-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,3-dihydro-indol-2-one,-   1-{(R)-2-[5-(2-Amino-pyridin-4-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-4H-benzo[1,4]oxazin-3-one,-   1-{(R)-2-[5-(6-Amino-pyridin-3-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   1-{(R)-2-[5-(1H-Benzoimidazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,-   N-(2-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,    and-   1-{(R)-2-[5-(2-Hydroxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,    and pharmaceutically acceptable salts and esters thereof.

It will be appreciated that the compounds of general formula (I) in thisinvention may be derivatised at functional groups to provide derivativeswhich are capable of conversion back to the parent compound in vivo.

The invention further relates to a process for the manufacture ofcompounds of formula (I) as defined above, which process comprisesreacting a compound of formula (II)

with a compound of formula (III)

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, and X are as defined in any ofclaims 1-22 and L is halogen.

The reaction of a compound of formula (II) with a compound of formula(III) can be carried out under conditions well known to the personskilled in the art. Such reactions can conveniently be carried out forexample by mixing a compound of formula (II) with e.g. an acid chlorideof formula (III) or alternatively with an activated ester thereof acompound of formula (III) in a solvent such as e.g. DMF at appropriatetemperatures between 25° C. and 120° C., optionally in the presence ofdiisopropylethylamine. Preferably, L is Cl. Alternatively, L can be anactive ester. Such active esters as well as their use to form amidebonds are well known to the person skilled in the art.

The present invention also relates to compounds of formula (I) asdefined above, when prepared by a process as described above.

The compounds of formula (I), (II) and (III) can be prepared by methodsknown in the art or as described below or in analogy thereto. Unlessotherwise indicated, R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and X are as describedabove.

Compounds of formula (I), can be prepared according to the followinggeneral methods.

Compounds of general formula 1 are dissolved preferably in DMF and 1equivalent of activation reagent such as TBTU is added. The reaction isstirred at room temperature for 10 min and the correspondinghydroxyamidine (compound 2) added to result in compounds of generalformula 3. The reaction mixture is heated to 80° C. and stirredovernight of treated under microwave conditions at 120° C. for 15-30minutes to result in 4. After evaporation of the solvent and extractedfrom ethylactate/water the crude material is treated with neattrifluoroacetic acid or 4N HCL in Dioxan to result in compounds ofgeneral formula 5. The final product is obtained by treating theseintermediates either with phenoxyl chloride and derivatives thereof orits corresponding active esters.

The corresponding N-methylpiperazine derivatives were generated from thepiperazines as indicated in scheme 2.

Compounds of type 1 are dissolved preferably in DMF and treated with anexcess of formaldehyde and catalytic amount of acetic acid. The reactionmixture is stirred at room temperature for 30 minutes and 1 equivalentof NaBH3CN added. The reaction is stirred at room temperature for 16 hand the product isolated by chromatography.

The carboxylic acid analogues were generated from the correspondingesters through classical saponification with NaOH or LiOH or bycatalytic debenzylation procedures where the starting material istypically dissolved in methanol and an aqueous solution of NaOH or LiOHis added.

The reaction is stirred preferably for 2 h at room temperature and theproduct extracted form ethylacetate/water after acidification of thereaction mixture.

The carboxyamide analogues were generated from the correspondingcarboxylates by preactivation with reagents such as TBTU in DMF. Thereaction mixtures are usually stirred at room temperature overnight.

The primary carboxyamide analogues were generated from the correspondingcarboxylates through coupling on Rink-resin and subsequent cleavage withTFA by preactivating the starting material with reagents such as TBTU.The reaction mixture is usually stirred at room temperature overnight.After excessive washing of the resins with solvents such as DMF,methanol and methylenchloride the solid phase material is treated withTFA at room temperature for 2 h. After evaporation the product isisolated by chromatography.

The amino derivatives were generated from the corresponding nitroanalogues through a Zink mediated reduction where the starting materialis dissolved preferably in ethanol and saturated aqueous ammoniumchloride. An excess of zinc powder is added, the reaction briefly heatedto reflux and then stirred at room temperature for 16 h. The product isisolated by extraction from ethylacetate/water and final chromatography

The following N-amides, -sulfonamides, -carbamates and -ureas were allgenerated from the corresponding amino-derivatives where theamino-derivatives are dissolved preferably in DMF and the correspondingacetyl chlorides or activate esters, sulfonyl chlorides or isocyanatesare added. The reactions proceed at room temperature. The products areisolated by chromatography.

The benzonitriles were generated from the corresponding primarybenzamides by treatment of the latter with neat trifluoroaceticanhydride at room temperature for preferably 16 h.

The non-commercially available aminoacids were generated fromPiperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester bycoupling with either acetyl chloride or methylsulfonyl chloride in THFat room temperature followed by saponification as described above.

The non-commercially available hydroxyamidines were generated from thecorresponding nitriles by the addition of 5 equivalents of hydroxylaminemono hydrochloride and 2.5 equivanents sodium carbonate in a mixture ofethanol/water (7:3). The reaction mixture was heated to 80° C. forusually 2 h. The product was isolated by extraction fromethylacetate/water.

The non-commercially available sulfonamido hydroxyamidines weregenerated by coupling of 4-cyanobenzen-1-sulfonylchloride with 2equivalents of the corresponding amine in THF at room temperature for 16h. After evaporation of the solvent the product is extracted fromethylacetate/water. The crude nitril is treated with hydrazine asdescribed above.

The non-commercially available 2-aminopyridino hydroxyamidines weregenerated from the corresponding nitrites as described above. Thenitriles were obtained from the corresponding chlorocyanopyridines afterdissolving in DMF and adding 2 equivalents of the amine. The reactionmixture was heated to 120° C. under microwave conditions usually for 30min. The product was isolated by extraction from ethylacetate/waterafter evaporation of the reaction solvent.

The aminoamidines were generated from the corresponding imidoethers byaddition of 1 equivalent of hydrazine monohydrate in methanol. Theproduct was isolated by precipitation when adding 1.25M HCl/methanol.The iminoethers were obtained from the corresponding nitriles aftersuspending in methylenchloride and saturation with HCl gas at 0° C. for30 min. The reaction mixture was stirred for 16 h at room temperatureand the product filtered off after addition of diethylether.

The non-commercially available nitrites were generated from thecorresponding primary amides by the addition of neat trifluoroaceticacidanhydride at room temperature preferably for 16 h.

Furthermore, as outlined in scheme 3, compounds of general formula 1 canbe dissolved preferably in DMF and 1 equivalent of activation reagentsuch as TBTU is added in addition to 1 equivalent of a base such asDIPEA. The reaction is cooled to 0° C. and an excess of hydrazine added.The reaction is warmed up and stirred at ambient temperature to resultin compound 2. After evaporation of the solvent and extraction fromethylactate/water the crude material is treated with 1 equivalent of thecorresponding amidine in DMF. Catalytic amount of acetic acid is addedand the reaction heated to 120° C. overnight to result in compounds ofgeneral formula 4. After evaporation of the solvent and extraction fromethylactate/water neat trifluoroacetic acid or 4N HCL in Dioxan is addedto generate compounds of general formula 5. The final product isobtained by treating these intermediates either with phenoxyacetylchloride and derivatives thereof or its corresponding active esters.

Furthermore, as outlined in scheme 4, compound 1 can be dissolvedpreferably in aqueous ethanol and treated with an excess of hydrazinehydrochloride and a base such as sodium carbonate to result in compound2. This intermediate can be coupled with 1 equivalent of pre-activatedcarboxylates or their corresponding acetyl chlorides in solvents such asDMF to result in compounds with the general formula 3. Cyclisation tothe corresponding oxadiazole occurs under elevated temperature eitherusing conventional or microwave heating. Boc cleavage is usuallyperformed using either neat TFA or 4N HCl in Dioxan to result incompounds of general formula 5. The final product is obtained bytreating these intermediates either with phenoxyacetyl chloride andderivatives thereof or its corresponding active esters.

The corresponding salts can be obtained by standard methods known to theperson skilled in the art, e.g. by dissolving the compound of formula(I)in a suitable solvent such as e.g. dioxan or THF and adding anappropriate amount of the corresponding acid. The products can usuallybe isolated by filtration or by chromatography.

The conversion of compounds of formula (I) into pharmaceuticallyacceptable esters can be carried out e.g. by treatment of a suitablecarboxy group present in the molecule with a suitable alcohol using e.g.a condensating reagent such asbenzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate(BOP), N,N-dicyclohexylcarbodiimide (DCC),N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) orO-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N,N-tetra-methyluronium-tetrafluorborate(TPTU). Pharmaceutically acceptable esters can furthermore be preparedby treatment of a suitable hydroxy group present in the molecule with asuitable acid, optionally or if necessary in the presence of acondensating agent as described above.

Insofar as their preparation is not described in the examples, thecompounds of formula (I) as well as all intermediate products can beprepared according to analogous methods or according to the methods setforth above. Starting materials are commercially available, known in theart or can be prepared by methods known in the art or in analogythereto.

As described above, the novel compounds of the present invention havebeen found to inhibit liver carnitine palmitoyl transferase 1 (L-CPT1)activity. The compounds of the present invention can therefore be usedin the treatment and/or prophylaxis of diseases which are modulated byL-CPT1 inhibitors, particularly diseases which are related tohyperglycemia and/or glucose tolerance disorders. Such diseases includee.g. diabetes and associated pathologies, non insulin dependent diabetesmellitus, obesity, hypertension, insulin resistance syndrome, metabolicsyndrome, hyperlipidemia, hypercholesterolemia, fatty liver disease,atherosclerosis, congestive heart failure and renal failure.

The invention therefore also relates to pharmaceutical compositionscomprising a compound as defined above and a pharmaceutically acceptablecarrier and/or adjuvant.

The invention likewise embraces compounds as described above for use astherapeutically active substances, especially as therapeutically activesubstances for the treatment and/or prophylaxis of diseases which aremodulated by L-CPT1 inhibitors, particularly as therapeutically activesubstances for the treatment and/or prophylaxis of hyperglycemia,glucose tolerance disorders, diabetes and associated pathologies, noninsulin dependent diabetes mellitus, obesity, hypertension, insulinresistance syndrome, metabolic syndrome, hyperlipidemia,hypercholesterolemia, fatty liver disease, atherosclerosis, congestiveheart failure and renal failure.

In another preferred embodiment, the invention relates to a method forthe therapeutic and/or prophylactic treatment of diseases which aremodulated by L-CPT1 inhibitors, particularly for the therapeutic and/orprophylactic treatment of hyperglycemia, glucose tolerance disorders,diabetes and associated pathologies, non insulin dependent diabetesmellitus, obesity, hypertension, insulin resistance syndrome, metabolicsyndrome, hyperlipidemia, hypercholesterolemia, fatty liver disease,atherosclerosis, congestive heart failure and renal failure, whichmethod comprises administering a compound as defined above to a humanbeing or animal.

The invention also embraces the use of compounds as defined above forthe therapeutic and/or prophylactic treatment of diseases which aremodulated by L-CPT1 inhibitors, particularly for the therapeutic and/orprophylactic treatment of hyperglycemia, glucose tolerance disorders,diabetes and associated pathologies, non insulin dependent diabetesmellitus, obesity, hypertension, insulin resistance syndrome, metabolicsyndrome, hyperlipidemia, hypercholesterolemia, fatty liver disease,atherosclerosis, congestive heart failure and renal failure.

The invention also relates to the use of compounds as described abovefor the preparation of medicaments for the therapeutic and/orprophylactic treatment of diseases which are modulated by L-CPT1inhibitors, particularly for the therapeutic and/or prophylactictreatment of hyperglycemia, glucose tolerance disorders, diabetes andassociated pathologies, non insulin dependent diabetes mellitus,obesity, hypertension, insulin resistance syndrome, metabolic syndrome,hyperlipidemia, hypercholesterolemia, fatty liver disease,atherosclerosis, congestive heart failure and renal failure. Suchmedicaments comprise a compound as described above.

Prevention and/or treatment of hyperglycemia and non insulin dependentdiabetes mellitus is the preferred indication.

The following tests were carried out in order to determine the activityof the compounds of the present invention. Background information on theperformed assays can be found in: Jackson et al., 1999, Biochem. J. 341,483-489 and Jackson et al., 2000, J. Biol. Chem. 275, 19560-19566.

Human liver and muscle CPT1 cDNAs and rat CPT2 cDNA were subcloned inpGAPZB or pGAPZA, respectively. These plasmids were used to transform P.pastoris strain X-33 via electroporation after the preparation ofelectrocompetent cells. High copy number clones were selected wherenecessary using 0.5 or 1 mg/ml Zeocin. Cultures for activitymeasurements were induced for 16 h in YPD medium (1% yeast extract, 2%peptone, 2% glucose). Crude cell extracts were prepared by disruptingthe cells with glass beads or French Press, depending on fermentersizes. After centrifugation, the cell-free extracts were resuspended incell breaking buffer (50 mM Tris, pH7.4, 100 mM KCl, 1 mM EDTA) in thepresence of a protease inhibitor cocktail, before aliquoting andfreezing at −20° C.

CPT activity was measured using a spectrophotometric assay using5,5′-dithio-bis-(2-nitrobenzoic acid) (DTNB) also called Ellman'sreagent. The HS-CoA released on the formation of acylcarnitine fromcarnitine (500 μM) and palmitoyl-CoA (80 μM) reduced DTNB (300 μM)forming 5-mercapto-(2-nitrobenzoic acid) which absorbed at 410 nm with amolar coefficient extinction of 13600 M⁻¹.cm⁻¹. The assay buffercontained 120 mM KCl, 25 mM Tris, pH 7.4, 1 mM EDTA. This assay was usedfor the identification of selective inhibitors of the liver CPT1 isoformversus the muscle CPT1 and CPT2 isoforms.

The compounds according to formula (I) preferably have an IC50 valuebelow 10 μM, preferably 10 nM to 10 μM, more preferably 10 nM to 5 μM.The following table shows data for some examples.

L-CPT1 inhibition Example IC₅₀ [μmol/l] 1 0.066 10 0.260 172 0.242

The compounds of formula I and/or their pharmaceutically acceptablesalts can be used as medicaments, e.g. in the form of pharmaceuticalpreparations for enteral, parenteral or topical administration. They canbe administered, for example, perorally, e.g. in the form of tablets,coated tablets, dragées, hard and soft gelatine capsules, solutions,emulsions or suspensions, rectally, e.g. in the form of suppositories,parenterally, e.g. in the form of injection solutions or suspensions orinfusion solutions, or topically, e.g. in the form of ointments, creamsor oils. Oral administration is preferred.

The production of the pharmaceutical preparations can be effected in amanner which will be familiar to any person skilled in the art bybringing the described compounds of formula I and/or theirpharmaceutically acceptable salts, optionally in combination with othertherapeutically valuable substances, into a galenical administrationform together with suitable, non-toxic, inert, therapeuticallycompatible solid or liquid carrier materials and, if desired, usualpharmaceutical adjuvants.

Suitable carrier materials are not only inorganic carrier materials, butalso organic carrier materials. Thus, for example, lactose, corn starchor derivatives thereof, talc, stearic acid or its salts can be used ascarrier materials for tablets, coated tablets, dragées and hard gelatinecapsules. Suitable carrier materials for soft gelatine capsules are, forexample, vegetable oils, waxes, fats and semi-solid and liquid polyols(depending on the nature of the active ingredient no carriers might,however, be required in the case of soft gelatine capsules). Suitablecarrier materials for the production of solutions and syrups are, forexample, water, polyols, sucrose, invert sugar and the like. Suitablecarrier materials for injection solutions are, for example, water,alcohols, polyols, glycerol and vegetable oils. Suitable carriermaterials for suppositories are, for example, natural or hardened oils,waxes, fats and semi-liquid or liquid polyols. Suitable carriermaterials for topical preparations are glycerides, semi-synthetic andsynthetic glycerides, hydrogenated oils, liquid waxes, liquid paraffins,liquid fatty alcohols, sterols, polyethylene glycols and cellulosederivatives.

Usual stabilizers, preservatives, wetting and emulsifying agents,consistency-improving agents, flavour-improving agents, salts forvarying the osmotic pressure, buffer substances, solubilizers, colorantsand masking agents and antioxidants come into consideration aspharmaceutical adjuvants.

The dosage of the compounds of formula I can vary within wide limitsdepending on the disease to be controlled, the age and the individualcondition of the patient and the mode of administration, and will, ofcourse, be fitted to the individual requirements in each particularcase. For adult patients a daily dosage of about 1 to 2000 mg,especially about 1 to 500 mg, comes into consideration. Depending onseverity of the disease and the precise pharmacokinetic profile thecompound could be administered with one or several daily dosage units,e.g. in 1 to 3 dosage units.

The pharmaceutical preparations conveniently contain about 1-500 mg,preferably 1-200 mg, of a compound of formula I.

The following Examples serve to illustrate the present invention in moredetail. They are, however, not intended to limit its scope in anymanner.

EXAMPLES Example 1(R)-1-{2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone

Step 1:

(R)-2-{[Hydroxyimino-(4-methoxy-phenyl)-methyl]-carbamoyl}-piperidine-1-carboxylicacid tert-butyl ester

23 mg (0.1 mmol) of Boc-D-Pipecolic Acid were treated with 0.1 mmol[Dimethylamino-([1,2,3]triazolo[4,5-b]pyridin-3-yloxy)-methylene]-dimethyl-ammoniumhexafluorophosphate (HATU) and Diisopropylamine (DIPEA) in 1 mlDimethylforamide (DMF) for 10 min. 17 mg (0.1 mmol) ofN-Hydroxy-4-methoxy-benzamidine were added and the reaction stirred atroom temperature for 20 min. The product was not further characterized.

Step 2:

(R)-2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidine-1-carboxylicacid tert-butyl ester

Crude material from step 1 was either treated at 80° C. for 16 h orbriefly heated to 120° C. under microwave conditions (10 min). The DMFwas evaporated and the product extracted from ethylacetate/water. Theproduct was not further characterized.

Step 3:

(R)-2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidinetrifluoroacetate

Crude material from step 2 was treated with neat trifluoroacetic acid(TFA) at room temperature for 1 h. The TFA was evaporated. The crudeproduct not further characterized.

Step 4:

(R)-1-{2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone

Crude material from step 3 was dissolved in 1 ml DMF and 0.1 mmol DIPEA.Either 0.1 mmol phenoxyacetyl chloride were added and the reactionstirred at room temperature for 30 min, or the correspondingphenoxyacetic acid derivatives were pre-activated with HATU/DIPEA in DMFfor lOmin and added to the crude material from step 3. The product wasisolated via preparative high performance liquid chromatography (HPLC).

MS(ISO): 394.4 (MH+)

The following compounds were prepared in analogy.

TABLE 1 MH⁺ Example Compound name Starting materials (found) 2(R)-3-(2-{2-[3-(4-Methoxy- Boc-D-Pipecolic Acid, N- 419.5phenyl)[1,2,4]oxadiazol-5-yl]- Hydroxy-4-methoxy-piperidin-1-yl}-2-oxo-ethoxy) benzamidine and 3- benzonitrileCyanophenoxy-acetyl chloride 3 (R)-1-{2-[3-(4-Methoxy- Boc-D-PipecolicAcid, N- 408.5 phenyl)-[1,2,4]oxadiazol-5-yl]- Hydroxy-4-methoxy-piperidin-1-yl}-2-phenoxy- benzamidine and 2-Phenoxy- propan-1-onepropionic acid 4 (R)-1-{2-[3-(4-Bromo-phenyl) Boc-D-Pipecolic Acid, N-442.2 [1,2,4]oxadiazol-5-yl]- Hydroxy-4-bromo-benzamidinepiperidin-1-yl}-2-phenoxy- and phenoxyacetyl chloride ethanone 5(R)-2-(4-Hydroxy-phenoxy)- Boc-D-Pipecolic Acid, N- 410.51-{2-[3-(4-methoxy-phenyl)- Hydroxy-4-methoxy- [1,2,4]oxadiazol-5-yl]-benzamidine and 4-Hydroxy- piperidin-1-yl}-ethanone phenoxyacetic acid 6(R)-2-(4-Chloro-phenoxy)-1- Boc-D-Pipecolic Acid, N- 428.5{2-[3-(4-methoxy-phenyl)- Hydroxy-4-methoxy- [1,2,4]oxadiazol-5-yl]-benzamidine and 4- piperidin-1-yl}-ethanone Chlorophenoxy-acetic acid 7(R)-2-(4-Hydroxymethyl- Boc-D-Pipecolic Acid, N- 424.2phenoxy)-1-{2-[3-(4-methoxy- Hydroxy-4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]- benzamidine and 4-piperidin-1-yl}-ethanone Hydroxymethylphenoxy-acetic acid 8(R)-2-(3-Chloro-phenoxy)-1- Boc-D-Pipecolic Acid, N- 428.5{2-[3-(4-methoxy-phenyl)- Hydroxy-4-methoxy- [1,2,4]oxadiazol-5-yl]-benzamidine and 3- piperidin-1-yl}-ethanone Chlorophenoxy-acetic acid 9(R)-2-(4-Fluoro-phenoxy)-1- Boc-D-Pipecolic Acid, N- 412.4{2-[3-(4-methoxy-phenyl)- Hydroxy-4-methoxy- [1,2,4]oxadiazol-5-yl]-benzamidine and 4- piperidin-1-yl}-ethanone Fluorophenoxy-acetic acid 10(R)-1-{2-[3-(4-Fluoro- Boc-D-Pipecolic Acid, N- 382.5phenyl)-[1,2,4]oxadiazol-5-yl]- Hydroxy-4-fluoro-benzamidinepiperidin-1-yl}-2-phenoxy- and phenoxyacetyl chloride ethanone 11(R)-1-{2-[3-(4-Methane- Boc-D-Pipecolic Acid, N- 442.5 sulfonyl-phenyl)-Hydroxy-4-methane- [1,2,4]oxadiazol-5-yl]- sulfonylbenzamidine andpiperidin-1-yl}-2-phenoxy- phenoxyacetyl chloride ethanone 12(R)-4-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 443.5acetyl)-piperidin-2-yl]- Hydroxy-4-sulfamoyl- [1,2,4]oxadiazol-3-yl}-benzamidine and phenoxyacetyl benzenesulfonamide chloride 13(R)-2-(4-Fluoro-phenoxy)-1- Boc-D-Pipecolic Acid, N- 383.4[2-(3-pyridin-4-yl- Hydroxy-isonicotinamidine and[1,2,4]oxadiazol-5-yl)- phenoxyacetyl chloride piperidin-1-yl]-ethanone14 (R)-3-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, 3-(N- 422.5acetyl)-piperidin-2-yl]- Hydroxycarbam-imidoyl)-[1,2,4]oxadiazol-3-yl}-benzoic benzoic acid methyl ester and acid methylester phenoxyacetyl chloride 15 (R)-1-{2-[3-(3-Nitro-phenyl)-Boc-D-Pipecolic Acid, N- 409.5 [1,2,4]oxadiazol-5-yl]-Hydroxy-3-nitro-benzamidine piperidin-1-yl}-2-phenoxy- and phenoxyacetylchloride ethanone 16 (R)-1-{2-[3-(4-Nitro-phenyl)- Boc-D-Pipecolic Acid,N- 409.5 [1,2,4]oxadiazol-5-yl]- Hydroxy-4-nitro-benzamidinepiperidin-1-yl}-2-phenoxy- and phenoxyacetyl chloride ethanone 17(R)-3-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 443.5acetyl)-piperidin-2-yl]- Hydroxy-3-sulfamoyl- [1,2,4]oxadiazol-3-yl}-benzamidine and phenoxyacetyl benzenesulfonamide chloride 18(R)-2-Phenoxy-1-[2-(3- Boc-D-Pipecolic Acid, N- 366.5pyrazin-2-yl-[1,2,4]oxadiazol- Hydroxy-pyrazine-2-5-yl)-piperidin-1-yl]-ethanone carboxamidine and phenoxyacetyl chloride19 (R)-1-(2-{3-[4-(Morpholine-4- Boc-D-Pipecolic Acid, N- 513.6sulfonyl)-phenyl]- Hydroxy-4-N-acetyl- [1,2,4]oxadiazol-5-yl}-benzamidine and phenoxyacetyl piperidin-1-yl)-2-phenoxy- chlorideethanone 20 (R)-1-{2-[3-(6-Methoxy- Boc-D-Pipecolic Acid, N- 395.5pyridin-3-yl)-[1,2,4]oxadiazol- Hydroxy-6-methoxy-5-yl]-piperidin-1-yl}-2- nicotinamidine and phenoxy-ethanonephenoxyacetyl chloride 21 (R)-1-{2-[3-(3- Boc-D-Pipecolic Acid, N- 394.5Hydroxymethyl-phenyl)- Hydroxy-3-hydroxymethyl [1,2,4]oxadiazol-5-yl]-benzamidine and phenoxyacetyl piperidin-1-yl}-2-phenoxy- chlorideethanone 22 (R)-6-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, 6-(N- 449.1acetyl)-piperidin-2-yl]- Hydroxycarb-amimidoyl)- [1,2,4]oxadiazol-3-yl}-nicotinic acid allyl ester and nicotinic acid allyl ester phenoxyacetylchloride 23 (R)-1-{2-[3-(4-Imidazol-1-yl- Boc-D-Pipecolic Acid, N- 430.5phenyl)-[1,2,4]oxadiazol-5-yl]- Hydroxy-4-imidazol-1-yl-piperidin-1-yl}-2-phenoxy- benzamidine and phenoxyacetyl ethanonechloride 24 (R)-N-Methyl-4-{5-[1-(2- Boc-D-Pipecolic Acid, N- 457.5phenoxy-acetyl)-piperidin-2- Hydroxy-4-methylsulfamoyl-yl]-[1,2,4]oxadiazol-3-yl}- benzamidine and phenoxyacetylbenzenesulfonamide chloride 25 (R)-1-{2-[3-(6-Morpholin-4-Boc-D-Pipecolic Acid, N- 450.5 yl-pyridin-3-yl)-Hydroxy-6-morpholin-4-yl- [1,2,4]oxadiazol-5-yl]- nicotinamidine andphenoxy- piperidin-1-yl}-2-phenoxy- acetyl chloride ethanone 26(R)-2-Phenoxy-1-{2-[3-(4- Boc-D-Pipecolic Acid, N- 496.5trifluoromethanesulfonyl- Hydroxy-4- phenyl)-[1,2,4]oxadiazol-5-yl]-trifluoromethanesulfonyl- piperidin-1-yl}-ethanone benzamidine andphenoxyacetyl chloride 27 (R)-2-Phenoxy-1-{2-[3-(4- Boc-D-PipecolicAcid, N- 432.5 trifluoromethyl-phenyl)- Hydroxy-4-trifluoromethyl-[1,2,4]oxadiazol-5-yl]- benzamidine and phenoxyacetylpiperidin-1-yl}-ethanone chloride 28 (R)-1-{2-[3-(4-Chloro-Boc-D-Pipecolic Acid, N- 398.4 phenyl)-[1,2,4]oxadiazol-5-yl]-Hydroxy-4-chloro-benzamidine piperidin-1-yl}-2-phenoxy- andphenoxyacetyl chloride ethanone 29 (R)-N-(4-{5-[1-(2-Phenoxy-Boc-D-Pipecolic Acid, N-[4-(N- 489.5 acetyl)-piperidin-2-yl]-Hydroxycarb-amimidoyl)-2- [1,2,4]oxadiazol-3-yl}-2-trifluoro-methyl-phenyl]- trifluoromethyl-phenyl)- acetamide andphenoxyacetyl acetamide chloride 30 (R)-1-{2-[3-(3- Boc-D-PipecolicAcid, N- 442.5 Methanesulfonyl-phenyl)- Hydroxy-3-methanesulfonyl-[1,2,4]oxadiazol-5-yl]- benzamidine and phenoxyacetylpiperidin-1-yl}-2-phenoxy- chloride ethanone 31 (R)-1-{2-[3-(4-Methyl-3-Boc-D-Pipecolic Acid, N- 423.5 nitro-phenyl)- Hydroxy-4-methyl-3-nitro-[1,2,4]oxadiazol-5-yl]- benzamidine and phenoxyacetylpiperidin-1-yl}-2-phenoxy- chloride ethanone 32(R)-1-{2-[3-(4-Methoxy-3- Boc-D-Pipecolic Acid, N- 439.5 nitro-phenyl)-Hydroxy-4-methoxy-3-nitro- [1,2,4]oxadiazol-5-yl]- benzamidine andphenoxyacetyl piperidin-1-yl}-2-phenoxy- chloride ethanone 33(R)-N-(2-Hydroxy-ethyl)-4- Boc-D-Pipecolic Acid, N- 487.5{5-[1-(2-phenoxy-acetyl)- Hydroxy-4-(2-hydroxy- piperidin-2-yl]-ethylsulfamoyl)-benzamidine [1,2,4]oxadiazol-3-yl}- and phenoxyacetylchloride benzenesulfonamide 34 (R)-N-(2-Methoxy-ethyl)-N-Boc-D-Pipecolic Acid, N- 515.5 methyl-4-{5-[1-(2-phenoxy-Hydroxy-4-[(2-methoxy-ethyl)- acetyl)-piperidin-2-yl]-methyl-suifamoyl]-benzamidine [1,2,4]oxadiazol-3-yl}- and phenoxyacetylchloride benzenesulfonamide 35 (R)-N,N-Dimethyl-4-{5-[1-(2-Boc-D-Pipecolic Acid, 4- 471.5 phenoxy-acetyl)-piperidin-2-Dimethylsulfamoyl-N-hydroxy- yl]-[1,2,4]oxadiazol-3-yl}- benzamidine andphenoxyacetyl benzenesulfonamide chloride 36 (R)-N,N-Diethyl-4-{5-[1-(2-Boc-D-Pipecolic Acid, 4- 499.6 phenoxy-acetyl)-piperidin-2-Diethylsulfamoyl-N-hydroxy- yl]-(1,2,4]oxadiazol-3-yl}- benzamidine andphenoxyacetyl benzenesulfonamide chloride 37 (R)-1-{2-[3-(2-Morpholin-4-Boc-D-Pipecolic Acid, N- 450.5 yl-pyridin-4-yl)-Hydroxy-2-morpholin-4-yl- [1,2,4]oxadiazol-5-yl]- isonicotinamidine andpiperidin-1-yl}-2-phenoxy- phenoxyacetyl chloride ethanone 38(R)-2-Phenoxy-1-{2-[3- Boc-D-Pipecolic Acid, N- 448.5(3,4,5,6-tetrahydro-2H- Hydroxy-3,4,5,6-tetrahydro-[1,2′]bipyridinyl-4′-yl)- 2H-[1,2′]bipyridinyl-4′-[1,2,4]oxadiazol-5-yl]- carboxamidine and piperidin-1-yl}-ethanonephenoxyacetyl chloride 39 (R)-2-Phenoxy-1-{2-[3-(2- Boc-D-PipecolicAcid, N- 466.5 thiomorpholin-4-yl-pyridin-4-Hydroxy-2-thiomorpholin-4-yl- yl)-[1,2,4]oxadiazol-5-yl]-isonicotinamidine and piperidin-1-yl}-ethanone phenoxyacetyl chloride 40(R)-1-{2-[3-(2-Diethylamino- Boc-D-Pipecolic Acid, 2- 436.5pyridin-4-yl)-[1,2,4]oxadiazol- Diethylamino-N-hydroxy-5-yl]-piperidin-1-yl}-2- isonicotin amidine and phenoxy-ethanonephenoxyacetyl chloride 41 (R)-4-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid,4-(N- 437.5 acetyl)-piperidin-2-yl]- Hydroxycarbamimidoyl)-[1,2,4]oxadiazol-3-yl}- pyridine-2-carboxylic acid ethylpyridine-2-carboxylic acid esterand phenoxyacetyl chloride ethyl ester42 (R)-1-(2-{3-[6-(4-Acetyl- Boc-D-Pipecolic Acid, 6-(4- 491.5piperazin-1-yl)-pyridin-3-yl]- Acetyl-piperazin-1yl)-N-[1,2,4]oxadiazol-5-yl}- hydroxy-nicotinamidine andpiperidin-1-yl)-2-phenoxy- phenoxyacetyl chloride ethanone 43(R)-1-{2-[3-(2-Imidazol-1-yl- Boc-D-Pipecolic Acid, N- 431.5pyridin-4-yl)-[1,2,4]oxadiazol- Hydroxy-2-imidazol-1-yl5-yl]-piperidin-1-yl}-2- isonicotinamidine and phenoxy-ethanonephenoxyacetyl chloride 44 (R)-1-(3-{5-[1-(2-Phenoxy- Boc-D-PipecolicAcid, N- 461.5 acetyl)-piperidin-2-y]- Hydroxy-3-(2-oxo-piperidin-1-[1,2,4]oxadiazol-3-yl}-phenyl)- yl)-benzamidine and phenoxy-piperidin-2-one acetyl chloride 45 (R)-1-(2-{3-[4-(3H-Imidazol-Boc-D-Pipecolic Acid, N- 430.5 4-yl)-phenyl]-[1,2,4]oxadiazol-Hydroxy-4-(3H-imidazol-4-yl)- 5-yl}-piperidin-1-yl)-2- benzamidine andphenoxy- phenoxy-ethanone acetyl chloride 46 (R)-1-(2-{3-[4-(2-Methyl-Boc-D-Pipecolic Acid, N- 444.5 imidazol-1-yl)-phenyl]-Hydroxy-4-(2-methyl-imidazol- [1,2,4]oxadiazol-5-yl}- 1-yl)-benzamidineand piperidin-1-yl)-2-phenoxy- phenoxy-acetyl chloride ethanone 47(R)-2-Phenoxy-1-{2-[3-(2- Boc-D-Pipecohc Acid, N- 431.5pyrazol-1-yl-pyridin-4-yl)- Hydroxy-2-pyrazol-1-yl-[1,2,4]oxadiazol-5-yl]- isonicotin amidine and piperidin-1-yl}-ethanonephenoxy-acetyl chloride 48 (R)-4-(5-{5-[1-(2-Phenoxy- Boc-D-PipecolicAcid, N- 463.5 acetyl)-piperidin-2-yl]- Hydroxy-6-(3-oxo-piperazin-1-[1,2,4]oxadiazol-3-yl}-pyridin- yl)-nicotinamidine and2-yl)-piperazin-2-one phenoxyacetyl chloride 49(R)-2-Phenoxy-1-(2-{3-[4- Boc-D-Pipecolic Acid, N- 430.1(M − H+)(1H-tetrazol-5-yl)-phenyl]- Hydroxy-4-(1H-tetrazol-5-yl)-[1,2,4]oxadiazol-5-yl}- benzamidine and phenoxyacetylpiperidin-1-yl)-ethanone chloride 50 (R)-1-{2-[3-(1H-Indazol-5-Boc-D-Pipecolic Acid, N- 404.5 yl)-[1,2,4]oxadiazol-5-yl]-Hydroxy-1H-indazole-5- piperidin-1-yl}-2-phenoxy- carboxamidine andethanone phenoxyacetyl chloride 51 (R)-1-{2-[3-(1H-Indazol-6-Boc-D-Pipecolic Acid, N- 404.1 yl)-[1,2,4]oxadiazol-5-yl]-Hydroxy-1H-indazole-5- piperidin-1-yl}-2-phenoxy- carboxamidine andethanone phenoxyacetyl chloride 52 (R)-1-{2-[3-(4-Fluoro-3-Boc-D-Pipecolic Acid, 4- 450.4 trifluoromethyl-phenyl)-Fluoro-N-hydroxy-3- [1,2,4]oxadiazol-5-yl]- trifluoromethyl-benzamidinepiperidin-1-yl}-2-phenoxy- and phenoxyacetyl chloride ethanone 53(R)-6-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 419.3acetyl)-piperidin-2-yl]- Hydroxy-2-oxo-2,3-dihydro-[1,2,4]oxadiazol-3-yl}-1,3- 1H-indole-6-carboxamidinedihydro-indol-2-one and phenoxyacetyl chloride 54(R)-5-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 420.4acetyl)-piperidin-2-yl]- Hydroxy-2-oxo-2,3-dihydro-[1,2,4]oxadiazol-3-yl}-1,3- 1H-benzoimidazole-5-dihydro-benzoimidazol-2-one carboxamidine and phenoxyacetyl chloride 55(R)-5-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 419.4acetyl)-piperidin-2-yl]- Hydroxy-2-oxo-2,3-dihydro-[1,2,4]oxadiazol-3-yl}-1,3- 1H-indole-5-carboxamidinedihydro-indol-2-one and phenoxyacetyl chloride 56(R)-1-{2-[3-(1H-Benzotriazol- Boc-D-Pipecolic Acid, N- 405.45-yl)-[1,2,4]oxadiazol-5-yl]- Hydroxy-1H-benzotriazole-5-piperidin-1-yl}-2-phenoxy- carboxamidine and ethanone phenoxyacetylchloride 57 (R)-1-{2-[3-(1H- Boc-D-Pipecolic Acid, N- 404.5Benzoimidazol-5-yl)- Hydroxy-1H-benzoimidazole-5-[1,2,4]oxadiazol-5-yl]- carboxamidine and piperidin-1-yl}-2-phenoxy-phenoxyacetyl chloride ethanone 58 (R)-1-(2-{3-[6-(1,1-Dioxo-Boc-D-Pipecolic Acid, 6-(1,1- 498.5 thiomorpholin-4-yl)-pyridin-Dioxo-thiomorpholin-4-yl)-N- 3-yl]-[1,2,4]oxadiazol-5-yl}-hydroxy-nicotinamidine and piperidin-1-yl)-2-phenoxy- phenoxyacetylchloride ethanone 59 (R)-N-(4-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid,N-[4-(N- 422.5 acetyl)-piperidin-2-yl]- Hydroxy-carbamimidoyl)-[1,2,4]oxadiazol-3-yl}-pyridin- pyridin-2-yl]-acetamide and2-yl)-acetamide phenoxyacetyl chloride 60 (R)-1-{2-[3-(6-Benzyloxy-Boc-D-Pipecolic Acid, 6- 470.8 pyridin-3-yl)-[1,2,4]oxadiazol-Benzyloxy-N-hydroxy- 5-yl]-piperidin-1-yl}-2- nicotinamidine andphenoxy-ethanone phenoxyacetyl chloride 61 (R)-5-{5-[1-(2-Phenoxy-Boc-D-Pipecolic Acid, 5-(N- 337.5 acetyl)-piperidin-2-yl]-Hydroxy-carbamimidoyl)- [1,2,4]oxadiazol-3-yl}- nicotinic acid ethylester and nicotinic acid ethyl ester phenoxyacetyl chloride 62(R)-4-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 381.5acetyl)-piperidin-2-yl]- Hydroxy-2-oxo-1,2-dihydro-[1,2,4]oxadiazol-3-yl}-1H- pyridine-4-carboxamidine and pyridin-2-onephenoxyacetyl chloride 63 (R)-5-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid,N- 381.5 acetyl)-piperidin-2-yl]- Hydroxy-6-oxo-1,6-dihydro-[1,2,4]oxadiazol-3-yl}-1H- pyridine-3-carboxamidine and pyridin-2-onephenoxyacetyl chloride 64 (R)-2-Phenoxy-1-[2-(5- Boc-D-Pipecolic Acid,N- 363.5 phenyl-2H-[1,2,4]triazol-3-yl)- Amino-benzamidine andpiperidin-1-yl]-ethanone phenoxyacetic acid 65 (R)-1-{2-[5-(4-Boc-D-Pipecolic Acid, N- 441.5 Methanesulfonyl-phenyl)-2H-Amino-4-methanesulfonyl- [1,2,4]triazol-3-yl]-piperidin- benzamidine andphenoxyacetic l-yl}-2-phenoxy-ethanone acid 66(R)-1-{2-[5-(3,4-Dimethoxy- Boc-D-Pipecolic Acid, N- 423.5phenyl)-2H-[1,2,4]triazol-3- Amino-3,4-Dimethoxy-yl]-piperidin-1-yl}-2-phenoxy- benzamidine and phenoxyacetic ethanoneacid 67 (R)-1-{2-[5-(3,4-Dichloro- Boc-D-Pipecolic Acid, N- 431.4phenyl)-2H-[1,2,4]triazol-3- Amino-3,4-Dichloro- yl]-piperidin-1-yl}-2-benzamidine and phenoxyacetic phenoxyethanone acid 68(R)-1-{2-[5-(4-Fluoro- Boc-D-Pipecolic Acid, N- 381.5phenyl)-2H-[1,2,4]triazol-3- Amino-4-Fluoro-benzamidineyl]-piperidin-1-yl}-2-phenoxy- and phenoxyacetic acid ethanone 69(R)-2-Phenoxy-1-{2-[5-(3- Boc-D-Pipecolic Acid, N- 431.5trifluoromethyl-phenyl)-2H- Amino-3-Trifluoromethyl-[1,2,4]triazol-3-yl]-piperidin- benzamidine and phenoxyacetic1-yl}-ethanone acid 70 (R)-1-{2-[5-(4-Methoxy- Boc-D-Pipecolic Acid, N-393.5 phenyl)-2H-[1,2,4]triazol-3- Amino-4-Methoxy-yl]-piperidin-1-yl}-2-phenoxy- benzamidine and phenoxyacetic ethanoneacid 71 (R)-1-{2-[5-(3-Nitro-phenyl)- Boc-D-Pipecolic Acid, N- 408.52H-[1,2,4]triazol-3-yl]- Amino-3-Nitro-benzamidinepiperidin-1-yl}-2-phenoxy- and phenoxyacetic acid ethanone 72(R)-3-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 421.5acetyl)-piperidin-2-yl]-1H- Amino-3-Benzoic [1,2,4]triazol-3-yl}-benzoicAcidmethylester-benzamidine acid methyl ester and phenoxyacetic acid 73(R)-1-{2-[5-(4-Fluoro-3- Boc-D-Pipecolic Acid, N- 449.0trifluoromethyl-phenyl)-2H- Amino-4-Fluoro-3-[1,2,4]triazol-3-yl]-piperidin- trifluoromethyl-benzamidine1-yl}-2-phenoxy-ethanone and phenoxyacetic acid 74(R)-6-{5-[1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 418.5acetyl)-piperidin-2-yl]-1H- Amino-2-Oxo-2,3-dihydro-1H-[1,2,4]triazol-3-yl}-1,3- indole-6-carboxamidine dihydro-indol-2-onebenzamidine and phenoxyacetic acid 75 1-{3-[3-(4-Methoxy-phenyl)-Morpholine-3,4-dicarboxylic 396.4 [1,2,4]oxadiazol-5-yl]- acid4-tert-butyl ester, N- morpholin-4-yl}-2-phenoxy- Hydroxy-4-methoxy-ethanone benzamidine and phenoxyacetyl chloride 761-{3-[3-(4-Methanesulfonyl- Morpholine-3,4-dicarboxylic 444.5phenyl)-[1,2,4]oxadiazol-5-yl]- acid 4-tert-butyl ester, N-morpholin-4-yl}-2-phenoxy- Hydroxy-4-methanesulfonyl- ethanonebenzamidine and phenoxyacetyl chloride 77 4-{5-[4-(2-Phenoxy-acetyl)-Morpholine-3,4-dicarboxylic 445.5 morpholin-3-yl]- acid 4-tert-butylester, N- [1,2,4]oxadiazol-3-yl}- Hydroxy-4-sulfamoyl-benzenesulfonamide benzamidine and phenoxyacetyl chloride 781-(3-{3-[6-(1,1-Dioxo- Morpholine-3,4-dicarboxylic 500.5thiomorpholin-4-yl)-pyridin- acid 4-tert-butyl ester, 6-(1,1-3-yl]-[1,2,4]oxadiazol-5-yl}- Dioxo-thiomorpholin-4-yl)-N-morpholin-4-yl)-2-phenoxy- hydroxy-nicotinamidine and ethanonephenoxyacetyl chloride 79 N-(4-{5-[4-(2-Phenoxy-Morpholine-3,4-dicarboxylic 424.6 acetyl)-morpholin-3-yl]- acid4-tert-butyl ester, N-[4-(N- [1,2,4]oxadiazol-3-yl}-pyridin-Hydroxycarbamimidoyl)- 2-yl)-acetamide pyridin-2-yl]-acetamide andphenoxyacetyl chloride 80 1-{3-[5-(4-Methanesulfonyl-Morpholine-3,4-dicarboxylic 443.4 phenyl)-2H-[1,2,4]triazol-3- acid4-tert-butyl ester, 4- yl]-morpholin-4-yl}-2- Methanesulfonyl-N-amino-phenoxy-ethanone benzamidine and phenoxyacetyl chloride 812-Phenoxy-1-{3-[5-(3- Morpholine-3,4-dicarboxylic 433.4trifluoromethyl-phenyl)-2H- acid 4-tert-butyl ester, 3-[1,2,4]triazol-3-yl]-morpholin- Trifluoromethyl-N-amino- 4-yl}-ethanonebenzamidine and phenoxyacetyl chloride 82 (R)-4-{5-[4-(2-Phenoxy-(R)-Morpholine-3,4- 383.4 acetyl)-morpholin-3-yl]- dicarboxylic acid4-tert-butyl [1,2,4]oxadiazol-3-yl}-1H- ester, N-Hydroxy-2-oxo-1,2-pyridin-2-one dihydro-pyridine-4- carboxamidine and phenoxyacetylchloride 83 1-{3-[3-(4-Methoxy-phenyl)- 4-(2-tert-Butoxy-acetyl)- 412.5[1,2,4]oxadiazol-5-yl]- thiomorpholine-3-carboxylicthiomorpholin-4-yl}-2- acid, N-Hydroxy-4-methoxy- phenoxy-ethanonebenzamidine and phenoxyacetyl chloride 84 1-{3-[3-(4-Methanesulfonyl-4-(2-tert-Butoxy-acetyl)- 460.4 phenyl)-[1,2,4]oxadiazol-5-yl]-thiomorpholine-3-carboxylic thiomorpholin-4-yl}-2- acid,N-Hydroxy-4-methane- phenoxy-ethanone sulfonyl-benzamidine andphenoxyacetyl chloride 85 4-{5-[4-(2-Phenoxy-acetyl)-4-(2-tert-Butoxy-acetyl)- 461.4 thiomorpholin-3-yl]-thiomorpholine-3-carboxylic [1,2,4]oxadiazol-3-yl}- acid,N-Hydroxy-4-sulfamoyl- benzenesulfonamide benzamidine and phenoxyacetylchloride 86 2-Phenoxy-1-[3-(3-pyridin-4- 4-(2-tert-Butoxy-acetyl)- 383.4yl-[1,2,4]oxadiazol-5-yl)- thiomorpholine-3-carboxylicthiomorpholin-4-yl]-ethanone acid, N-Hydroxy-isonicotinamidine andphenoxyacetyl chloride 87 1-{2-[3-(4-Methoxy-phenyl)-Piperazine-1,3-dicarboxylic acid 395.5 [1,2,4]oxadiazol-5-yl]-1-tert-butyl ester, N-Hydroxy- piperazin-1-yl}-2-phenoxy-4-methoxy-benzamidine and ethanone phenoxyacetic acid 88N-(5-{5-[1-(2-Phenoxy- Piperazine-1,3-dicarboxylic acid 423.5acetyl)-piperazin-2-yl]- 1-tert-butyl ester, N-[5-(N-[1,2,4]oxadiazol-3-yl}-pyridin- Hydroxycarbamimidoyl)- 2-yl)-acetamidepyridin-2-yl]-acetamide and phenoxyacetic 89 1-{2-[3-(2-Imidazol-1-yl-Piperazine-1,3-dicarboxylic acid 432.5 pyridin-4-yl)-[1,2,4]oxadiazol-1-tert-butyl ester, N-Hydroxy- 5-yl]-piperazin-1-yl}-2- 2-imidazol-1-yl-phenoxy-ethanone isonicotinamidine and phenoxyacetic 90N,N-Diethyl-4-{5-[1-(2- Piperazine-1,3-dicarboxylic acid 500.5phenoxy-acetyl)-piperazin-2- 1-tert-butyl ester, 4-yl]-[1,2,4]oxadiazol-3-yl}- Diethylsulfamoyl-N- benzenesulfonamidehydroxybenzamidine and phenoxyacetic acid 91 N,N-Dimethyl-4-{5-[1-(2-Piperazine-1,3-dicarboxylic acid 472.5 phenoxy-acetyl)-piperazin-2-1-tert-butyl ester, 4- yl]-[1,2,4]oxadiazol-3-yl}- Dimethylsulfamoyl-N-benzenesulfonamide hydroxybenzamidine and phenoxyacetic acid 924-{5-[1-(2-Phenoxy-acetyl)- Piperazine-1,3-dicarboxylic acid 444.4piperazin-2-yl]- 1-tert-butyl ester, N-Hydroxy- [1,2,4]oxadiazol-3-yl}-4-sulfamoyl-benzamidine and benzenesulfonamide phenoxyacetic acid 931-{2-[3-(4-Methanesulfonyl- Piperazine-1,3-dicarboxylic acid 443.5phenyl)-[1,2,4]oxadiazol-5-yl]- 1-tert-butyl ester, N-Hydroxy-piperazin-1-yl}-2-phenoxy- 4-methane-sulfonyl- ethanone benzamidine andphenoxyacetic acid 94 2-Phenoxy-1-[2-(3-pyridin-4-Piperazine-1,3-dicarboxylic acid 366.4 yl-[1,2,4]oxadiazol-5-yl)-1-tert-butyl ester, N- piperazin-1-yl]-ethanoneHydroxyisonicotin-amidine and phenoxyacetic acid 951-{2-[3-(2,4-Dichloro-phenyl)- Piperazine-1,3-dicarboxylic acid 433.3[1,2,4]oxadiazol-5-yl]- 1-tert-butyl ester, 2,4-Dichloro-piperazin-1-yl}-2-phenoxy- N-hydroxy-benzamidine and ethanonephenoxyacetic acid 96 2-Phenoxy-1-[2-(3-pyridin-2-Piperazine-1,3-dicarboxylic acid 366.4 yl-[1,2,4]oxadiazol-5-yl)-1-tert-butyl ester, N-Hydroxy- piperazin-1-yl]-ethanonepyridine-2-carboxamidine and phenoxyacetic acid 972-Phenoxy-1-[2-(3-pyridin-2- Piperazine-1,3-dicarboxylic acid 366.4yl-[1,2,4]oxadiazol-5-yl)- 1-tert-butyl ester, N-Hydroxy-piperazin-2-yl]-ethanone pyridine-3-carboxamidine and phenoxyacetic acid98 1-{2-[3-(4-Nitro-phenyl)- Piperazine-1,3-dicarboxylic acid 410.4[1,2,4]oxadiazol-5-yl]- 1-tert-butyl ester, N-Hydroxy-piperazin-1-yl}-2-phenoxy- 4-nitro-benzamidine nd ethanone phenoxyaceticacid 99 1-{2-[3-(6-Methoxy-pyridin-3- Piperazine-1,3-dicarboxylic acid396.4 yl)-[1,2,4]oxadiazol-5-yl]- 1-tert-butyl ester, N-Hydroxy-piperazin-1-yl}-2-phenoxy- 6-methoxy-nicotinamidine and ethanonephenoxyacetic acid 100 1-{2-[3-(6-Morpholin-4-yl-Piperazine-1,3-dicarboxylic acid 451.5 pyridin-3-yl)-[1,2,4]oxadiazol-1-tert-butyl ester, N-Hydroxy- 5-yl]-piperazin-1-yl}-2-6-morpholin-4-yl- phenoxy-ethanone nicotinamidine and phenoxy aceticacid 101 1-{2-[3-(6-Morpholin-4-yl- Piperazine-1,3-dicarboxylic acid367.4 pyridin-3-yl)-[1,2,4]oxadiazol- 1-tert-butyl ester, N-Hydroxy-5-yl]-piperazin-1-yl}-2- pyrazine-2-carboxamidine and phenoxy-ethanonephenoxy-acetic acid 102 1-{2-[3-(3-Hydroxymethyl-Piperazine-1,3-dicarboxylic acid 395.4 phenyl)-[1,2,4]oxadiazol-5-yl]-1-tert-butyl ester, N-Hydroxy- piperazin-1-yl}-2-phenoxy-3-hydroxy-methyl-benzamidine ethanone and phenoxy-acetic acid 1031-{2-[3-(4-Diethylamino- Piperazine-1,3-dicarboxylic acid 436.5phenyl)-[1,2,4]oxadiazol-5-yl]- 1-tert-butyl ester, 4-piperazin-1-yl}-2-phenoxy- Diethylamino-N-hydroxy- ethanone benzamidineand phenoxy- acetic acid 104 1-(2-{3-[4-(Morpholine-4-Piperazine-1,3-dicarboxylic acid 514.6 sulfonyl)-phenyl]- 1-tert-butylester, N-Hydroxy- [1,2,4]oxadiazol-5-yl}- 4-(morpholine-4-sulfonyl)-piperazin-1-yl)-2-phenoxy- benzamidine and phenoxyacetic ethanone acid105 N-Methyl-4-{5-[1-(2-phenoxy- Piperazine-1,3-dicarboxylic acid 458.4acetyl)-piperazin-2-yl]- 1-tert-butyl ester, N-Hydroxy-[1,2,4]oxadiazol-3-yl}- 4-methylsulfamoyl- benzenesulfonamidebenzamidine and phenoxyacetic acid 106 N-(2-Methoxy-ethyl)-N-Piperazine-1,3-dicarboxylic acid 516.4 methyl-4-{5-[1-(2-phenoxy-1-tert-butyl ester, N-Hydroxy- acetyl)-piperazin-2-yl]-4-[(2-methoxy-ethyl)-methyl- [1,2,4]oxadiazol-3-yl}-sulfamoyl]-benzamidine and benzenesulfonamide phenoxy-acetic acid 1071-{2-[3-(4-Chloro-phenyl)- Piperazine-1,3-dicarboxylic acid 399.3[1,2,4]oxadiazol-5-yl]- 1-tert-butyl ester, 4-Chloro-N-piperazin-1-yl}-2-phenoxy- hydroxy-benzamidine and ethanonephenoxyacetic acid 108 N-(4-{5-[1-(2-Phenoxy-Piperazine-1,3-dicarboxylic acid 490.4 acetyl)-piperazin-2-yl]-1-tert-butyl ester, N-[4-(N- [1,2,4]oxadiazol-3-yl}-2-Hydroxycarbamimidoyl)-2- trifluoromethyl-phenyl)-trifluoro-methyl-phenyl]- acetamide acetamide and phenoxyacetic acid 1094-{5-[1-(2-Phenoxy-acetyl)- Piperazine-1,3-dicarboxylic acid 449.4piperazin-2-yl]- 1-tert-butyl ester, 4-(N-[1,2,4]oxadiazol-3-yl}-benzoic Hydroxycarbamimidoyl)- acid allyl esterbenzoic acid allyl ester and phenoxyacetic acid 1101-{2-[3-(4-Methyl-3-nitro- Piperazine-1,3-dicarboxylic acid 424.4phenyl)-[1,2,4]oxadiazol-5-yl]- 1-tert-butyl ester, N-Hydroxy-piperazin-1-yl}-2-phenoxy- 4-methyl-3-nitro-benzamidine ethanone andphenoxyacetic acid 111 1-{2-[3-(4-Methoxy-3-nitro-Piperazine-1,3-dicarboxylic acid 440.4 phenyl)-[1,2,4]oxadiazol-5-yl]-1-tert-butyl ester, N-Hydroxy- piperazin-1-yl}-2-phenoxy-4-methoxy-3-nitro- ethanone benzamidine and phenoxyacetic acid 1121-{2-[3-(4-Chloro-3-nitro- Piperazine-1,3-dicarboxylic acid 444.8phenyl)-[1,2,4]oxadiazol-5-yl]- 1-tert-butyl ester, 4-Chloro-N-piperazin-1-yl}-2-phenoxy- hydroxy-3-nitro-benzamidine ethanone andphenoxyacetic acid 113 3-Fluoro-4-{5-[1-(2-phenoxy-Piperazine-1,3-dicarboxylic acid 441.4 acetyl)-piperazin-2-yl]-1-tert-butyl ester, 3-Fluoro-4- [1,2,4]oxadiazol-3-yl}-benzoic(N-hydroxy-carbamimidoyl)- acid methyl ester benzoic acid methyl esterand phenoxyacetic acid 114 4-{5-[1-(2-Phenoxy-acetyl)-Piperazine-1,3-dicarboxylic acid 438.4 piperazin-2-yl]- 1-tert-butylester, 4-(N- [1,2,4]oxadiazol-3-yl}- Hydroxycarbamimidoyl)-pyridine-2-carboxylic acid pyridine-2-carboxylic acid ethyl ethyl esterester and phenoxyacetic acid 115 2-Phenoxy-1-{2-[3-(4-Piperazine-1,3-dicarboxylic acid 448.5 piperidin-1-yl-phenyl)-1-tert-butyl ester, N-Hydroxy- [1,2,4]oxadiazol-5-yl]-4-piperidin-1-yl-benzamidine piperazin-1-yl}-ethanone and phenoxyaceticacid 116 1-{2-[3-(4-Morpholin-4-yl- Piperazine-1,3-dicarboxylic acid450.4 phenyl)-[1,2,4]oxadiazol-5-yl]- 1-tert-butyl ester, N-Hydroxy-piperazin-1-yl}-2-phenoxy- 4-morpholin-4-yl-benzamidine ethanone andphenoxyacetic acid 117 1-(2-{3-[4-(2-Methyl- Piperazine-1,3-dicarboxylicacid 445.4 imidazol-1-yl)-phenyl]- 1-tert-butyl ester, N-Hydroxy-[1,2,4]oxadiazol-5-yl}- 4-(2-methyl-imidazol-1-yl)-piperazin-1-yl)-2-phenoxy- benzamidine and phenoxyacetic ethanone acid118 1-(2-{3-[4-(3H-Imidazol-4- Piperazine-1,3-dicarboxylic acid 431.4yl)-phenyl]-[1,2,4]oxadiazol-5- 1-tert-butyl ester, N-Hydroxy-yl}-piperazin-1-yl)-2-phenoxy- 4-(3H-imidazol-4-yl)- ethanonebenzamidine and phenoxyacetic acid 119 4-(5-{5-[1-(2-Phenoxy-acetyl)-Piperazine-1,3-dicarboxylic acid 464.4 piperazin-2-yl]- 1-tert-butylester, N-Hydroxy- [1,2,4]oxadiazol-3-yl}-pyridin-6-(3-oxo-piperazin-1-yl)- 2-yl)-piperazin-2-one nicotinamidine andphenoxyacetic acid 120 1-{2-[3-(6-Imidazol-1-yl-Piperazine-1,3-dicarboxylic acid 432.4 pyridin-3-yl)-[1,2,4]oxadiazol-1-tert-butyl ester, N-Hydroxy- 5-yl]-piperazin-1-yl}-2-6-imidazol-1-yl-nicotinamidine phenoxy-ethanone and phenoxyacetic acid121 1-(2-{3-[6-(4-Acetyl- Piperazine-1,3-dicarboxylic acid 492.4piperazin-1-yl)-pyridin-3-yl]- 1-tert-butyl ester, 6-(4-Acetyl-[1,2,4]oxadiazol-5-yl}- piperazin-1-yl)-N-hydroxy-piperazin-1-yl)-2-phenoxy- nicotinamidine and ethanone phenoxyaceticacid 122 2-Phenoxy-1-{2-[3-(4-pyrrol- Piperazine-1,3-dicarboxylic acid430.4 1-yl-phenyl)-[1,2,4]oxadiazol- 1-tert-butyl ester, N-Hydroxy-5-yl]-piperazin-1-yl}-ethanone 4-pyrrol-1-yl-benzamidine andphenoxyacetic acid 123 2-Phenoxy-1-{2-[3-(4 Piperazine-1,3-dicarboxylicacid 497.4 trifluoromethanesulfonyl- 1-tert-butyl ester, N-Hydroxy-phenyl)-[1,2,4]oxadiazol-5-yl]- 4-trifluoromethane-sulfonyl-piperazin-1-yl}-ethanone benzamidine and phenoxyacetic acid 1241-{2-[3-(2-Morpholin-4-yl- Piperazine-1,3-dicarboxylic acid 451.4pyridin-4-yl)-[1,2,4]oxadiazol- 1-tert-butyl ester, N-Hydroxy-5-yl]-piperazin-1-yl}-2- 2-morpholin-4-yl- phenoxy-ethanoneisonicotinamidine and phenoxyacetic acid 125 2-Phenoxy-1-{2-[3-(2-Piperazine-1,3-dicarboxylic acid 467.4 thiomorpholin-4-yl-pyridin-4-1-tert-butyl ester, N-Hydroxy- yl)-[1,2,4]oxadiazol-5-yl]-2-thiomorpholin-4-yl- piperazin-1-yl}-ethanone isonicotinamidine andphenoxyacetic acid 126 1-(2-{3-[6-(3-Hydroxymethyl-Piperazine-1,3-dicarboxylic acid 465.4 pyrrolidin-1-yl)-pyridin-3-yl]-1-tert-butyl ester, N-Hydroxy- [1,2,4]oxadiazol-5-yl}-6-(3-hydroxymethyl-pyrrolidin- piperazin-1-yl)-2-phenoxy-1-yl)-nicotinamidine and ethanone phenoxyacetic acid 127(R)-1-{2-[3-(6-Methoxy- D-Piperazine-1,3-dicarboxylic 396.4pyridin-3-yl)-[1,2,4]oxadiazol- acid 1-tert-butyl ester, N-5-yl]-piperazin-1-yl}-2- Hydroxy-6-methoxy- phenoxy-ethanonenicotinamidine and phenoxyacetic acid 128 (R)-1-{2-[3-(6-Morpholin-4-D-Piperazine-1,3-dicarboxylic 451.4 yl-pyridin-3-yl)- acid 1-tert-butylester, N- [1,2,4]oxadiazol-5-yl]- Hydroxy-6-morpholin-4-yl-piperazin-1-yl}-2-phenoxy- nicotinamidine and ethanone phenoxyaceticacid 129 (R)-N-(4-{5-[1-(2-Phenoxy- D-Piperazine-1,3-dicarboxylic 490.4acetyl)-piperazin-2-yl]- acid 1-tert-butyl ester, N-[4-(N-[1,2,4]oxadiazol-3-yl}-2- Hydroxycarbamimidoyl)-2-trifluoromethyl-phenyl)- trifluoromethyl-phenyl]- acetamide acetamideand phenoxyacetic acid 130 (R)-1-{2-[3-(4-Methyl-3-D-Piperazine-1,3-dicarboxylic 424.4 nitro-phenyl)- acid 1-tert-butylester, N- [1,2,4]oxadiazol-5-yl]- Hydroxy-4-methyl-3-nitro-piperazin-1-yl}-2-phenoxy- benzamidine and phenoxyacetic ethanone acid131 (R)-1-{2-[3-(4-Methyl-3- D-Piperazine-1,3-dicarboxylic 440.4nitro-phenyl)- acid 1-tert-butyl ester, 1-{2-[3- [1,2,4]oxadiazol-5-yl]-(4-Methoxy-3-nitro-phenyl)- piperazin-1-yl}-2-phenoxy-[1,2,4]oxadiazol-5-yl]- ethanone piperazin-1-yl}-2-phenoxy- ethanone andphenoxyacetic acid 132 (R)-1-{2-[3-(4-Morpholin-4-D-Piperazine-1,3-dicarboxylic 450.4 yl-phenyl)-[1,2,4]oxadiazol-5- acid1-tert-butyl ester, N- yl]-piperazin-1-yl}-2-phenoxy-Hydroxy-4-morpholin-4-yl- ethanone benzamidine and phenoxyacetic acid133 (R)-1-(2-{3-[4-(3H-Imidazol- D-Piperazine-1,3-dicarboxylic 431.44-yl)-phenyl]-[1,2,4]oxadiazol- acid 1-tert-butyl ester, N-5-yl}-piperazin-1-yl)-2- Hydroxy-4-(3H-imidazol-4-yl)- phenoxy-ethanonebenzamidine and phenoxyacetic acid 134 (R)-1-(2-{3-[6-(3-D-Piperazine-1,3-dicarboxylic 465.4 Hydroxymethyl-pyrrolidin-1- acid1-tert-butyl ester, N- yl)-pyridin-3-yl]- Hydroxy-6-(3-hydroxymethyl-[1,2,4]oxadiazol-5-yl}- pyrrolidin-1-yl)-nicotinamidinepiperazin-1-yl)-2-phenoxy- and phenoxyacetic acid ethanone 135(R)-1-(2-{3-[6-(4-Acetyl- D-Piperazine-1,3-dicarboxylic 492.5piperazin-1-yl)-pyridin-3-yl]- acid 1-tert-butyl ester, 6-(4-[1,2,4]oxadiazol-5-yl}- Acetyl-piperazin-1-yl)-N-piperazin-1-yl)-2-phenoxy- hydroxy-nicotinamidine and ethanonephenoxyacetic acid 136 (R)-N-(3-{5-[1-(2-Phenoxy-D-Piperazine-1,3-dicarboxylic 422.4 acetyl)-piperazin-2-yl]- acid1-tert-butyl ester, N-[3-(N- [1,2,4]oxadiazol-3-yl}-phenyl)-Hydroxycarbamimidoyl)- acetamide hydrochloride phenyl]-acetamide andphenoxyacetic acid 137 (R)-1-{2-[3-(1H- D-Piperazine-1,3-dicarboxylic405.5 Benzoimidazol-5-yl)- acid 1-tert-butyl ester, N-[1,2,4]oxadiazol-5-yl]- Hydroxy-1H-benzoimidazole-5-piperazin-1-yl}-2-phenoxy- carboxamidine and ethanone phenoxyacetic acid138 (R)-1-{2-[3-(1H-Benzotriazol- D-Piperazine-1,3-dicarboxylic 406.45-yl)-[1,2,4]oxadiazol-5-yl]- acid 1-tert-butyl ester, N-piperazin-1-yl}-2-phenoxy- Hydroxy-1H-benzotriazole-5- ethanonecarboxamidine and phenoxyacetic acid 139 (R)-1-{2-[3-(1H-Indazol-5-D-Piperazine-1,3-dicarboxylic 405.4 yl)-[1,2,4]oxadiazol-5-yl]- acid1-tert-butyl ester, N- piperazin-1-yl}-2-phenoxy- Hydroxy-1H-indazole-5-ethanone hydrochloride carboxamidine and phenoxyacetic acid 140(R)-5-{5-[1-(2-Phenoxy- D-Piperazine-1,3-dicarboxylic 421.5acetyl)-piperazin-2-yl]- acid 1-tert-butyl ester, N-[1,2,4]oxadiazol-3-yl}-1,3- Hydroxy-2-oxo-2,3-dihydro-dihydro-benzoimidazol-2-one 1H-benzoimidazole-5- carboxamidine andphenoxyacetic acid 141 (R)-1-(2-{3-[6-(1,1-Dioxo-D-Piperazine-1,3-dicarboxylic 499.1 thiomorpholin-4-yl)-pyridin- acid1-tert-butyl ester, 6-(1,1- 3-yl]-[1,2,4]oxadiazol-5-yl}-Dioxo-thiomorpholin-4-yl)-N- piperazin-1-yl)-2-phenoxy-hydroxy-nicotinamidine and ethanone hydrochloride phenoxyacetic acid 142(R)-1-{2-[3-(3-Nitro-phenyl)- D-Piperazine-1,3-dicarboxylic 410.1[1,2,4]oxadiazol-5-yl]- acid 1-tert-butyl ester, N-piperazin-1-yl}-2-phenoxy- Hydroxy-3-nitro-benzamidine ethanone andphenoxyacetic acid 143 (R)-1-{2-[3-(4-Fluoro-D-Piperazine-1,3-dicarboxylic 383.4 phenyl)-[1,2,4]oxadiazol-5-yl]- acid1-tert-butyl ester, 4-Fluoro- piperazin-1-yl}-2-phenoxy-N-hydroxy-benzamidine and ethanone phenoxyacetic acid 144(R)-4-{5-[1-(2-Phenoxy- D-Piperazine-1,3-dicarboxylic 382.4acetyl)-piperazin-2-yl]- acid 1-tert-butyl ester, N-[1,2,4]oxadiazol-3-yl}-1H- Hydroxy-2-oxo-1,2-dihydro- pyridin-2-onepyridine-4-carboxamidine and phenoxyacetic acid 1451-{4-Acetyl-2-[3-(4-methoxy- 4-Acetyl-piperazine-1,2- 437.5phenyl)-[1,2,4]oxadiazol-5-yl]- dicarboxylic acid 1-tert-butylpiperazin-1-yl}-2-phenoxy- ester, N-Hydroxy-4-methoxy- ethanonebenzamidine and phenoxyacetic acid 146 1-{4-Acetyl-2-[3-(4-4-Acetyl-piperazine-1,2- 485.5 methanesulfonyl-phenyl)- dicarboxylicacid 1-tert-butyl [1,2,4]oxadiazol-5-yl]- ester, N-Hydroxy-4-piperazin-1-yl}-2-phenoxy- methanesulfonyl-benzamidine ethanone andphenoxyacetic acid 147 4-{5-[4-Acetyl-1-(2-phenoxy-4-Acetyl-piperazine-1,2- 486.5 acetyl)-piperazin-2-yl]- dicarboxylicacid 1-tert-butyl [1,2,4]oxadiazol-3-yl}- ester, N-Hydroxy-4-sulfamoyl-benzenesulfonamide benzamidine and phenoxyacetic acid 1481-[4-Acetyl-2-(3-pyridin-4-yl- 4-Acetyl-piperazine-1,2- 408.5[1,2,4]oxadiazol-5-yl)- dicarboxylic acid 1-tert-butylpiperazin-1-yl]-2-phenoxy- ester, N-Hydroxy- ethanone isonicotinamidineand phenoxyacetic acid 149 1-{4-Methanesulfonyl-2-[3-(4-4-Methanesulfonyl-piperazine- 473.2 methoxy-phenyl)- 1,2-dicarboxylicacid 1-tert- [1,2,4]oxadiazol-5-yl]- butyl ester, N-Hydroxy-4-piperazin-1-yl}-2-phenoxy- Methoxy-benzamidine and ethanonephenoxyacetic acid 150 (R)-1-{2-[5-(4-Fluoro-D-Piperazine-1,3-dicarboxylic 382.4 phenyl)-2H-[1,2,4]triazol-3- acid1-tert-butyl ester, 4-Fluoro- yl]-piperazin-1-yl}-2-phenoxy-N-amino-benzamidine and ethanone phenoxyacetic acid 151(R)-2-Phenoxy-1-{2-[5-(3- D-Piperazine-1,3-dicarboxylic 432.4trifluoromethyl-phenyl)-2H- acid 1-tert-butyl ester, 3-[1,2,4]triazol-3-yl]-piperazin- Trifluoromethyl-N-amino- 1-yl}-ethanonebenzamidine and phenoxyacetic acid 152 1-{2-[5-(4-Fluoro-3-Piperazine-1,3-dicarboxylic acid 450.4 trifluoromethyl-phenyl)-2H-1-tert-butyl ester, 4-Fluoro-3- [1,2,4]triazol-3-yl]-piperazin-trifluoromethyl-N-amino- 1-yl}-2-phenoxy-ethanone benzamidine andphenoxyacetic acid 153 1-{2-[5-(4-Methanesulfonyl-Piperazine-1,3-dicarboxylic acid 442.4 phenyl)-2H-[1,2,4]triazol-3-1-tert-butyl ester, 4- yl]-piperazin-1-yl}-2-phenoxy-Methanesulfonyl-N-amino- ethanone benzamidine and phenoxyacetic acid 1542-Phenoxy-1-{2-[5-(3- Piperazine-1,3-dicarboxylic acid 432.4trifluoromethyl-phenyl)-2H- 1-tert-butyl ester, 3-[1,2,4]triazol-3-yl]-piperazin- Trifluoromethyl-N-amino- 1-yl}-ethanonebenzamidine and phenoxyacetic acid 155 2-Phenoxy-1-[2-(5-p-tolyl-2H-Piperazine-1,3-dicarboxylic acid 378.4 [1,2,4]triazol-3-yl)-piperazin-1-tert-butyl ester, 4-Methyl-N- 1-yl]-ethanone amino-benzamidine andphenoxyacetic acid 156 2-Phenoxy-1-{2-[5-(4 Piperazine-1,3-dicarboxylicacid 432.4 trifluoromethyl-phenyl)-2H- 1-tert-butyl ester, 4-[1,2,4]triazol-3-yl]-piperazin- Trifluoromethyl-N-amino- 1-yl}-ethanonebenzamidine and phenoxyacetic acid 157 1-{2-[5-(4-Methoxy-phenyl)-Piperazine-1,3-dicarboxylic acid 394.4 2H-[1,2,4]triazol-3-yl]-1-tert-butyl ester, 4-Methoxy- piperazin-1-yl}-2-phenoxy-N-amino-benzamidine and ethanone phenoxyacetic acid 1581-{2-[5-(4-Fluoro-phenyl)-2H- Piperazine-1,3-dicarboxylic acid 382.4[1,2,4]triazol-3-yl]-piperazin- 1-tert-butyl ester, 4-Fluoro-N-1-yl}-2-phenoxy-ethanone amino-benzamidine and phenoxyacetic acid 1591-{2-[5-(4-Fluoro-phenyl)-2H- Piperazine-1,3-dicarboxylic acid 400.4[1,2,4]triazol-3-yl]-piperazin- 1-tert-butyl ester, 2,4-Difluoro-1-yl}-2-phenoxy-ethanone N-amino-benzamidine and phenoxyacetic acid 1601-{2-[5-(3,4-Dimethoxy- Piperazine-1,3-dicarboxylic acid 424.4phenyl)-2H-[1,2,4]triazol-3- 1-tert-butyl ester, 3,4-yl]-piperazin-1-yl}-2-phenoxy- Dimethoxy-N-amino- ethanone benzamidineand phenoxyacetic acid 161 1-{2-[5-(3,4-Dichloro-phenyl)-Piperazine-1,3-dicarboxylic acid 432.4 2H-[1,2,4]triazol-3-yl]-1-tert-butyl ester, 3,4-Dichioro- piperazin-1-yl}-2-phenoxy-N-amino-benzamidine and ethanone phenoxyacetic acid 1621-{2-[5-(2-Fluoro-phenyl)-2H- Piperazine-1,3-dicarboxylic acid 382.4[1,2,4]triazol-3-yl]-piperazin- 1-tert-butyl ester, 3-Fluoro-N-1-yl}-2-phenoxy-ethanone amino-benzamidine and phenoxyacetic acid 1631-{2-[5-(2-Fluoro-phenyl)-2H- Piperazine-1,3-dicarboxylic acid 382.4[1,2,4]triazol-3-piperazin- 1-tert-butyl ester, 2-Fluoro-N-1-yl}-2-phenoxy-ethanone amino-benzamidine and phenoxyacetic acid

Example 1644-{5-[4-Methyl-1-(2-phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide

0.1 mmol of4-{5-[1-(2-Phenoxy-acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamideare dissolved in 1 ml DMF and 1 eq. DIPEA and Na₂CO₃ added. To thesuspension 1 eq. of MeI is added and the reaction stirred at roomtemperature overnight. The product is isolated via preparative HPLC.

MS(ISO): 422.4 (MH+)

The following compounds have been prepared in analogy:

TABLE 2 MH⁺ Example Compound name Starting material (found) 165(R)-1-{2-[3-(1H-Indazol-5yl)- (R)-1-{2-[3-(1H-Indazol-5 yl)- 419.5[1,2,4]oxadiazol-5-yl]-4- [1,2,4]oxadiazol-5 yl]-methyl-piperazin-1-yl}-2- piperazin-1-yl}-2-phenoxy- phenoxy-ethanoneethanone 166 (R)-1-{2-[3-(4-Fluoro-phenyl)- (R)-1-{2-[3-(4-Fluoro- 397.4[1,2,4]oxadiazol-5-yl]-4- phenyl)-[1,2,4]oxadiazol-5-yl]-methyl-piperazin-1-yl}-2- piperazin1-yl}-2-phenoxy- phenoxy-ethanoneethanone 167 (R)-5-{5-[4-Methyl-1-(2- (R)-5-{5-[1-(2-Phenoxy- 434.5phenoxy-acetyl)-piperazin-2- acetyl)-piperazin-2-yl]-yl]-[1,2,4]oxadiazol-3-yl}-1,3- [1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one dihydro-indol-2-one 168 (R)-5-{5-[4-Methyl-1-(2-(R)-5-{5-[1-(2-Phenoxy- 435.5 phenoxy-acetyl)-piperazin-2-acetyl)-piperazin-2-yl]- yl]-[1,2,4]oxadiazol-3-yl}-1,3-[1,2,4]oxadiazol-3-yl}-1,3- dihydro-benzoimidazol-2-onedihydro-benzoimidazol-2-one 169 (R)-1-{2-[3-(1H- (R)-1-{2-[3-(1H- 419.5Benzoimidazol-5-yl)- Benzoimidazol-5-yl)- [1,2,4]oxadiazol-5-yl]-4-[1,2,4]oxadiazol-5-yl]- methyl-piperazin-1-yl}-2-piperazin-1-yl}-2-phenoxy- phenoxy-ethanone ethanone 170(R)-1-{2-[3-(1H-Benzotriazol- (R)-1-{2-[3-(1H-Benzotriazol- 420.55-yl)-[1,2,4]oxadiazol-5-yl]-4- 5-yl)-[1,2,4]oxadiazol-5-yl]-methyl-piperazin-1-yl}-2- piperazin-1-yl}-2-phenoxy- phenoxy-ethanoneethanone 171 (R)-1-{4-Methyl-2-[5-(3- (R)-2-Phenoxy-1-{2-[5-(3- 446.4trifluoromethyl-phenyl)-2H- trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperazin-1- [1,2,4]triazol-3-yl]-piperazinyl}-2-phenoxy-ethanone 1-yl}-ethanone 172 (R)-1-{2-[5-(4-Methoxy-(R)-1-{2-[5-(4-Methoxy- 408.4 phenyl)-2H-[1,2,4]triazol-3-yl]-phenyl)-2H-[1,2,4]triazol-3- 4-methyl-piperazin-1-yl}-2-yl]-piperazin}-yl}-2-phenoxy- phenoxy-ethanone ethanone 173(R)-1-{2-[5-(4-Fluoro-phenyl)- (R)-1-{2-[5-(4-Fluoro- 396.42H-[1,2,4]triazol-3-yl]-4- phenyl)-2H-[1,2,4]triazol-3-methyl-piperazin-1-yl}-2- yl]-piperazin1-yl}-2-phenoxy- phenoxy-ethanoneethanone 174 (R)-1-{2-[5-(4- (R)-1-{2-[5-(4- 456.4Methanesulfonyl-phenyl)-2H- Methanesulfonyl-phenyl)-2H-[1,2,4]triazol-3-yl]-4-methyl- [1,2,4]triazol-3-yl]-piperazin-piperazin-1-yl}-2-phenoxy- 1-yl}-2-phenoxy-ethanone ethanone 175(R)-4-{5-[4-Methyl-1-(2- (R)-4-{5-[1-(2-Phenoxy- 436.5phenoxy-acetyl)-piperazin-2- acetyl)-piperazin-2-yl]-1H-yl]-1H-[1,2,4]triazol-3-yl}- [1,2,4]triazol-3-yl}-benzoic benzoic acidmethyl ester acid methyl ester 176 (R)-N-(3-{5-[4-Methyl-1-(2-(R)-N-(3-{5-[1-(2-Phenoxy- 435.5 phenoxy-acetyl)-piperazin-2-acetyl)-piperazin-2-yl]-1H- yl]-1H-[1,2,4]triazol-3-yl}-[1,2,4]triazol-3-yl}-phenyl)- phenyl)-acetamide acetamide 177(R)-N-(3-{5-[4-Methyl-1-(2- (R)-N-(3-{5-[1-(2-Phenoxy- 471.5phenoxy-acetyl)-piperazin-2- acetyl)-piperazin-2-yl]-1H-yl]-1H-[1,2,4]triazol-3-yl}- [1,2,4]triazol-3-yl}-phenyl)phenyl)-methanesulfonamide methanesulfonamide 178(R)-4-{5-[4-Methyl-1-(2- (R)-4-{5-[1-(2-Phenoxy- 421.5phenoxy-acetyl)-piperazin-2- acetyl)-piperazin-2-yl]-1H-yl]-1H-[1,2,4]triazol-3-yl}- [1,2,4]triazol-3-yl}-benzamide benzamide

Example 179(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoicacid

4 mmol of(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoicacid benzyl ester were dissolved in MeOH and treated with Pd/C andflushed with hydrogen (3 bar) and stirred for 30 min. The catalyst wasfiltered off and the solvent evaporated. After extraction fromethylacetate/water the resulting oil was purified via preperative HPLC.The corresponding alkylesters were treated with aq. 2N NaOH or LiOH inmethanol at room temperature. The allylester can be cleaved usingPd(Ph3)4 as catalyst and morpholine as a nucleophile.

MS(ISO): 408.5 (MH+)

The following compounds have been prepared in analogy:

TABLE 3 MH⁺ Example Compound name Starting material (found) 180(R)-3-{5-[1-(2-Phenoxy- (R)-3-{5-[1-(2-Phenoxy- 408.5acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic [1,2,4]oxadiazol-3-yl}-benzoic acid acidmethyl ester 181 (R)-6-{5-[1-(2-Phenoxy- (R)-6-{5-[1-(2-Phenoxy- 409.4acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinic [1,2,4]oxadiazol-3-yl}-nicotinic acidacid methylester 182 (R)-2-Fluoro-4-{5-[1-(2- (R)-2-Fluoro-4-{5-[1-(2-426.5 phenoxy-acetyl)-piperidin-2- phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- yl]-[1,2,4]oxadiazol-3-yl}- benzoic acidbenzoic acid methyl ester 183 (R)-5-{5-[1-(2-Phenoxy-(R)-5-{5-[1-(2-Phenoxy- 409.4 acetyl)-piperidin-2-yl]-acetyl)-piperidin-2-yl]- [1,2,4]oxadiazol-3-yl}-pyridine-[1,2,4]oxadiazol-3-yl}- 2-carboxylic acid pyridine-2-carboxylic acidmethyl ester 184 (R)-4-{5-[1-(2-Phenoxy- (R)-4-{5-[1-(2-Phenoxy- 409.4acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine- [1,2,4]oxadiazol-3-yl}- 2-carboxylicacid pyridine-2-carboxylic acid ethyl ester 185 (R)-3-{5-[1-(2-Phenoxy-(R)-3-{5-[1-(2-Phenoxy- 407.4 acetyl)-piperidin-2-yl]-1H-acetyl)-piperidin-2-yl]-1H- [1,2,4]triazol-3-yl}-benzoic acid[1,2,4]triazol-3-yl}-benzoic acid methyl ester 1863-{5-[4-(2-Phenoxy-acetyl)- 3-{5-[4-(2-Phenoxy-acetyl)- 410.5morpholin-3-yl]- morpholin-3-yl]- [1,2,4]oxadiazol-3-yl}-benzoic[1,2,4]oxadiazol-3-yl}-benzoic acid acid methyl ester 1873-{5-[4-(2-Phenoxy-acetyl)- 3-{5-[4-(2-Phenoxy-acetyl)- 410.5morpholin-3-yl]- morpholin-3-yl]- [1,2,4]oxadiazol-3-yl}-benzoic[1,2,4]oxadiazol-3-yl}-benzoic acid acid methyl ester 1884-{5-[4-(2-Phenoxy-acetyl)- 4-{5-[4-(2-Phenoxy-acetyl)- 426.4thiomorpholin-3-yl]- thiomorpholin-3-yl]- [1,2,4]oxadiazol-3-yl}-[1,2,4]oxadiazol-3-yl}- benzamide benzamide methyl ester 1894-{5-[4-(2-Phenoxy-acetyl)- 4-{5-[4-(2-Phenoxy-acetyl)- 426.4thiomorpholin-3-yl]- thiomorpholin-3-yl}- [1,2,4]oxadiazol-4-yl}-[1,2,4]oxadiazol-4-yl}- benzamide benzamide methyl ester 1903-{5-[4-Acetyl-1-(2-phenoxy- 3-{5-[4-Acetyl-1-(2-phenoxy- 451.5acetyl)-piperazin-2-yl]- acetyl)-piperazin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoic [1,2,4]oxadiazol-3-yl}-benzoic acid acidmethyl ester 191 4-{5-[4-Acetyl-1-(2-phenoxy-4-{5-[4-Acetyl-1-(2-phenoxy- 451.5 acetyl)-piperazin-2-yl]-acetyl)-piperazin-2-yl]- [1,2,4]oxadiazol-3-yl}-benzoic[1,2,4]oxadiazol-3-yl}-benzoic acid acid methyl ester 192(R)-4-{5-[4-Methyl-1-(2- (R)-4-{5-[1-(2-Phenoxy- 422.5phenoxy-acetyl)-piperazin-2- acetyl)-piperazin-2-yl]-1H-yl]-1H-[1,2,4]triazol-3-yl}- [1,2,4]triazol-3-yl}-benzoic acid benzoicacid methyl ester 193 (R)-5-{5-[1-(2-Phenoxy- (R)-5-{5-[1-(2-Phenoxy-409.5 acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinic [1,2,4]oxadiazol-3-yl}-nicotinic acidacid ethyl ester

Example 194(R)-1-(2-{3-[4-(Morpholine-4-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone

0.07 mmol of(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoicacid were treated with 1 eq. of TBTU/DIPEA in 1 ml DMF for 10 min and 2eq. of Morpholine added. Ther reaction is stirred overnight at roomtemperature and the product isolated via preperative HPLC.

MS(ISO): 477.6 (MH+)

The following compounds have been prepared in analogy:

TABLE 4 MH⁺ Example Compound name Starting material (found) 195(R)-1-(2-{3-[4-(3-Hydroxy- (R)-4-{5-[1-(2-Phenoxy- 477.6pyrrolidine-1-carbonyl)- acetyl)-piperidin-2-yl]-phenyl]-[1,2,4]oxadiazol-5-yl}- [1,2,4]oxadiazol-3-yl}-benzoicpiperidin-1-yl)-2-phenoxy- acid and pyrrolidin-3-ol ethanone 196(R)-N,N-Diethyl-4-{5-[1-(2- (R)-4-{5-[1-(2-Phenoxy- 463.6phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand diethylamine 197 (R)-N-Methyl-4-{5-[1-(2- (R)-4-{5-[1-(2-Phenoxy-421.5 phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand methylamine 198 (R)-N,N-Dimethyl-4-{5-[1-(2- (R)-4-{5-[1-(2-Phenoxy-435.5 phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand dimethylamine 199 (R)-N-Ethyl-4-{5-[1-(2- (R)-4-{5-[1-(2-Phenoxy-435.5 phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand ethylamine 200 (R)-N-Cyclopropyl-4-{5-[1-(2- (R)-4-{5-[1-(2-Phenoxy-447.5 phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand cyclopropylamine 201 (R)-N-(2-Hydroxy-ethyl)-4-{5-(R)-4-{5-[1-(2-Phenoxy- 451.5 [1-(2-phenoxy-acetyl)-acetyl)-piperidin-2-yl]- piperidin-2-yl]-[1,2,4]oxadiazol-[1,2,4]oxadiazol-3-yl}-benzoic 3-yl}-benzamide acid and ethanolamine 202(R)-N-(2-Methoxy-ethyl)-N- (R)-4-{5-[1-(2-Phenoxy- 479.5methyl-4-{5-[1-(2-phenoxy- acetyl)-piperidin-2-yl]-acetyl)-piperidin-2-yl]- [1,2,4]oxadiazol-3-yl}-benzoic[1,2,4]oxadiazol-3-yl}- acid and (2-methoxy-ethyl)- benzamidemethyl-amine 203 (R)-N-Methyl-3-{5-[1-(2- (R)-3-{5-[1-(2-Phenoxy- 421.5phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand methylamine 204 (R)-N,N-Dimethyl-3-{5-[1-(2- (R)-3-{5-[1-(2-Phenoxy-435.5 phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand dimethylamine 205 (R)-N-Ethyl-3-{5-[1-(2- (R)-3-{5-[1-(2-Phenoxy-435.5 phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand ethylamine 206 (R)-N-Cyclopropyl-3-{5-[1-(2- (R)-3-{5-[1-(2-Phenoxy-447.5 phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand cyclopropylamine 207 (R)-N-(2-Hydroxy-ethyl)-3-{5-(R)-3-{5-[1-(2-Phenoxy- 451.5 [1-(2-phenoxy-acetyl)-acetyl)-piperidin-2-yl]- piperidin-2-yl]-[1,2,4]oxadiazol-[1,2,4]oxadiazol-3-yl}-benzoic 3-yl}-benzamide acid and ethanolamine 208(R)-N-(2-Methoxy-ethyl)-N- (R)-3-{5-[1-(2-Phenoxy- 479.5methyl-3-{5-[1-(2-phenoxy- acetyl)-piperidin-2-yl]-acetyl)-piperidin-2-yl]- [1,2,4]oxadiazol-3-yl}-benzoic[1,2,4]oxadiazol-3-yl}- acid and (2-methoxy-ethyl)- benzamidemethyl-amine 209 (R)-1-(2-{3-[3-(Morpholine-4- (R)-3-{5-[1-(2-Phenoxy-477.6 carbonyl)-phenyl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-piperidin- [1,2,4]oxadiazol-3-yl}-benzoic1-yl)-2-phenoxy-ethanone acid and morpholine 210(R)-1-(2-{3-[3-(3-Hydroxy- (R)-3-{5-[1-(2-Phenoxy- 477.6pyrrolidine-1-carbonyl)- acetyl)-piperidin-2-yl]-phenyl]-[1,2,4]oxadiazol-5-yl}- [1,2,4]oxadiazol-3-yl}-benzoicpiperidin-1-yl)-2-phenoxy- acid and pyrrolidin-3-ol ethanone 211(R)-N,N-Diethyl-3-{5-[1-(2- (R)-3-{5-[1-(2-Phenoxy- 463.6phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-benzoic benzamide acidand diethylamine 212 (R)-4-{5-[1-(2-Phenoxy-acetyl)-(R)-4-{5-[1-(2-Phenoxy- 422.5 piperidin-2-yl]-[1,2,4]oxadiazol-acetyl)-piperidin-2-yl]- 3-yl}-pyridine-2-carboxylic acid[1,2,4]oxadiazol-3-yl}- methylamide pyridine-2-carboxylic acid andmethylamine 213 (R)-4-{5-[1-(2-Phenoxy-acetyl)- (R)-4-{5-[1-(2-Phenoxy-436.5 piperidin-2-yl]-[1,2,4]oxadiazol- acetyl)-piperidin-2-yl]-3-yl}-pyridine-2-carboxylic acid [1,2,4]oxadiazol-3-yl}- dimethylamidepyridine-2-carboxylic acid and dimethylamine 214(R)-4-{5-[1-(2-Phenoxy-acetyl)- (R)-4-{5-[1-(2-Phenoxy- 436.5piperidin-2-yl]-[1,2,4]oxadiazol- acetyl)-piperidin-2-yl]-3-yl}-pyridine-2-carboxylic acid [1,2,4]oxadiazol-3-yl}- ethylamidepyridine-2-carboxylic acid and ethylamine 215(R)-4-{5-[1-(2-Phenoxy-acetyl)- (R)-4-{5-[1-(2-Phenoxy- 464.5piperidin-2-yl]-[1,2,4]oxadiazol- acetyl)-piperidin-2-yl]-3-yl}-pyridine-2-carboxylic acid [1,2,4]oxadiazol-3-yl}- diethylamidepyridine-2-carboxylic acid and diethylamine 216(R)-1-(2-{3-[2-(Morpholine-4- (R)-4-{5-[1-(2-Phenoxy- 478.5carbonyl)-pyridin-4-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-piperidin- [1,2,4]oxadiazol-3-yl}-1-yl)-2-phenoxy-ethanone pyridine-2-carboxylic acid and morpholine 217(R)-1-(2-{3-[2-(3- (R)-4-{5-[1-(2-Phenoxy- 540.5Methanesulfonyl-pyrrolidine-1- acetyl)-piperidin-2-yl]-carbonyl)-pyridin-4-yl]- [1,2,4]oxadiazol-3-yl}-[1,2,4]oxadiazol-5-yl}-piperidin- pyridine-2-carboxylic acid and1-yl)-2-phenoxy-ethanone 3-methanesulfonyl-pyrrolidine 218(R)-5-{5-[1-(2-Phenoxy-acetyl)- (R)-5-{5-[1-(2-Phenoxy- 422.4piperidin-2-yl]-[1,2,4]oxadiazol- acetyl)-piperidin-2-yl]-3-yl}-pyridine-2-carboxylic acid [1,2,4]oxadiazol-3-yl}- methylamidepyridine-2-carboxylic acid and methylamine 219 (R)-N-Methyl-3-{5-[1-(2-(R)-3-{5-[1-(2-Phenoxy- 420.4 phenoxy-acetyl)-piperidin-2-yl]-acetyl)-piperidin-2-yl]-1H- 1H-[1,2,4]triazol-3-yl}-[1,2,4]triazol-3-yl}-benzoic benzamide acid and methylamine 2201N,N-Diethyl-4-{5-[1-(2- 3-[3-(4-Carboxy-phenyl)- 464.3phenoxy-acetyl)-piperazin-2-yl]- [1,2,4]oxadiazol-5-yl]-4-(2-[1,2,4]oxadiazol-3-yl}- phenoxy-acetyl)-piperazine-1- benzamidecarboxylic acid tert-butyl ester and diethylamine 2211-(2-{3-[4-(Morpholine-4- 3-[3-(4-Carboxy-phenyl)- 478.0carbonyl)-phenyl]- [1,2,4]oxadiazol-5-yl]-4-(2-[1,2,4]oxadiazol-5-yl}-piperazin- phenoxy-acetyl)-piperazine-1-1-yl)-2-phenoxy-ethanone carboxylic acid tert-butyl ester and morpholine222 N-Methyl-4-{5-[1-(2-phenoxy- 3-[3-(4-Carboxy-phenyl)- 422.4acetyl)-piperazin-2-yl]- [1,2,4]oxadiazol-5-yl]-4-(2-[1,2,4]oxadiazol-3-yl}- phenoxy-acetyl)-piperazine-1- benzamidecarboxylic acid tert-butyl ester and methylamine 223(R)-N-Methyl-5-{5-[1-(2- (R)-5-{5-[1-(2-Phenoxy- 422.4phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-nicotinic nicotinamideacid and methylamine 224 (R)-N-Ethyl-5-{5-[1-(2- (R)-5-{5-[1-(2-Phenoxy-436.5 phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-nicotinic nicotinamideacid and ethylamine 225 (R)-N-Diethyl-5-{5-[1-(2-(R)-5-{5-[1-(2-Phenoxy- 436.5 phenoxy-acetyl)-piperidin-2-yl]-acetyl)-piperidin-2-yl]- [1,2,4]oxadiazol-3-yl}-[1,2,4]oxadiazol-3-yl}-nicotinic nicotinamide acid and diethylamine 226(R)-N-Diethyl-5-{5-[1-(2- (R)-5-{5-[1-(2-Phenoxy- 464.5phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-nicotinic nicotinamideacid and diethylamine 227 (R)-N-(2-Hydroxy-ethyl)-5-{5-(R)-5-{5-[1-(2-Phenoxy- 452.5 [1-(2-phenoxy-acetyl)-acetyl)-piperidin-2-yl]- piperidin-2-yl]-[1,2,4][1,2,4]oxadiazol-3-yl}-nicotinic oxadiazol-3-yl}-nicotinamide acid andaminoethanol 228 (R)-N-(2-Methoxy-ethyl)-N- (R)-5-{5-[1-(2-Phenoxy-480.6 methyl-5-{5-[1-(2-phenoxy- acetyl)-piperidin-2-yl]-acetyl)-piperidin-2-yl]- [1,2,4]oxadiazol-3-yl}-nicotinic[1,2,4]oxadiazol-3-yl}- acid and (2-Methoxy-ethyl)- nicotinamidemethyl-amine 229 (R)-N-Cyclopropyl-5-{5-[1-(2- (R)-5-{5-[1-(2-Phenoxy-448.5 phenoxy-acetyl)-piperidin-2-yl]- acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}- [1,2,4]oxadiazol-3-yl}-nicotinic nicotinamideacid and cyclopropylamine 230 (R)-1-(2-{3-[5-(3-Hydroxy-(R)-5-{5-[1-(2-Phenoxy- 478.5 pyrrolidine-1-carbonyl)-pyridin-acetyl)-piperidin-2-yl]- 3-yl]-[1,2,4]oxadiazol-5-yl}-[1,2,4]oxadiazol-3-yl}-nicotinic piperidin-1-yl)-2-phenoxy- acid andPyrrolidin-3-ol ethanone

Example 231(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide

34 mg of(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoicacid were treated with 1 eq HATU/DIPEA in DMF and added to 1 eq ofRink-Resin. The reaction was shaken overnight at room temperature. Theresin was washed with DMF, MeOH, DCM (3 times each) and then treatedwith TFA/DCM (1:1) for 2 h. The resulting yellow oil was purified viapreparative HPLC.

MS(ISO): 407.5 (MH+)

The following compounds have been prepared in analogy:

TABLE 5 MH⁺ Example Compound name Starting materials (found) 232(R)-3-{5-[1-(2-Phenoxy-acetyl)- (R)-3-{5-[1-(2-Phenoxy- 407.4piperidin-2-yl]-[1,2,4]oxadiazol- acetyl)-piperidin-2-yl]-3-yl}-benzamide [1,2,4]oxadiazol-3-yl}-benzoic acid and Rink resin 233(R)-4-{5-[1-(2-Phenoxy-acetyl)- (R)-4-{5-[1-(2-Phenoxy- 408.4piperidin-2-yl]-[1,2,4]oxadiazol- acetyl)-piperidin-2-yl]-3-yl}-pyridine-2-carboxylic acid [1,2,4]oxadiazol-3-yl}- amidepyridine-2-carboxylic acid and Rink resin 234(R)-3-{5-[1-(2-Phenoxy-acetyl)- (R)-3-{5-[1-(2-Phenoxy- 406.4piperidin-2-yl]-1H-[1,2,4]triazol- acetyl)-piperidin-2-yl]-1H-3-yl}-benzamide [1,2,4]triazol-3-yl}-benzoic acid and Rink resin 2354-{5-[4-(2-Phenoxy-acetyl)- 4-{5-[4-(2-Phenoxy-acetyl)- 409.5morpholin-3-yl]- morpholin-3-yl]- [1,2,4]oxadiazol-3-yl}-benzamide[1,2,4]oxadiazol-3-yl}-benzoic acid and Rink resin 2364-{5-[4-(2-Phenoxy-acetyl)- 4-{5-[4-(2-Phenoxy-acetyl)- 425.5thiomorpholin-3 yl]- thiomorpholin-3 yl]-[1,2,4]oxadiazol-3yl}-benzamide [1,2,4]oxadiazol-3yl}-benzoic acid andRink resin 237 4-{5-[1-(2-Phenoxy-acetyl)- 3-[3-(4-Carboxy-phenyl)-408.3 piperazin-2-yl]-[1,2,4]oxadiazol- [1,2,4]oxadiazol-5-yl]-4-(2-3-yl}-benzamide phenoxy-acetyl)-piperazine-1- carboxylic acid tert-butylester and Rink resin 238 (R)-5-{5-[1-(2-Phenoxy-acetyl)-(R)-5-{5-[1-(2-Phenoxy- 408.5 piperidin-2-yl]-[1,2,4]oxadiazol-acetyl)-piperidin-2-yl]- 3-yl}-nicotinamide[1,2,4]oxadiazol-3-yl}-nicotinic acid and Rink resin

Example 239(R)-1-{2-[3-(3-Amino-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone

(R)-1-{2-[3-(3-Nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanonewere dissolved in 100 ml MeOH. 50 ml sat. NH₄Cl and Zn-powder wereadded. The suspension was briefly heated to reflux and stirred for 30min. After filtration the MeOH was evaporated and the product isolatedvia extraction ethylacetate/water.

MS(ISO): 379.5 (MH+)

Example 240(R)-1-{2-[3-(4-Amino-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone

(R)-1-{2-[3-(4-Nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanonewere dissolved in 100 ml MeOH. 50 ml sat. NH₄Cl and Zn-powder wereadded. The suspension was briefly heated to reflux and stirred for 30min. After filtration the MeOH was evaporated and the product isolatedvia extraction ethylacetate/water.

MS(ISO): 379.5 (MH+)

Example 241(R)-1-{2-[5-(3-Amino-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone

(R)-1-{2-[5-(3-Nitro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanonewere dissolved in 100 ml MeOH. 50 ml sat. NH₄Cl and Zn-powder wereadded. The suspension was briefly heated to reflux and stirred for 30min. After filtration the MeOH was evaporated and the product isolatedvia extraction ethylacetate/water.

MS(ISO): 378.5 (MH+)

Example 242(R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide

1 mmol(R)-1-{2-[3-(3-Amino-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxyethanone were dissolved in THF. 2 eq. of DIPEA were added. The reactionwas cooled to 0° C. 1 eq. of acetylchloride in THF was added dropwiseand the reaction stirred for 30 min. The product was isolated byextraction from ethylactetade/water and subsequent purification viapreparative HPLC.

MS(ISO): 421.5 (MH+)

The following compounds have been generated in analogy by using eitheracetyl chloride, mesylchloride, chloroformic acid allyl ester orethylisocyanate as the reagent:

TABLE 6 MH⁺ Example Compound name Starting materials (found) 243(R)-N-(4-{5-[1-(2-Phenoxy- (R)-1-{2-[3-(4-Amino-phenyl)- 421.5acetyl)-piperidin-2-yl]- [1,2,4]oxadiazol-5-yl]-piperidin-[1,2,4]oxadiazol-3-yl}-phenyl)- 1-yl}-2-phenoxy-ethanone and acetamideacetyl chloride 244 (R)-N-(5-{5-[1-(2-Phenoxy-(R)-1-{2-[3-(6-Amino-pyridin- 422.5 acetyl)-piperidin-2-yl]-3-yl)-[1,2,4]oxadiazol-5-yl]- [1,2,4]oxadiazol-3-yl}-pyridin-piperidin-1-yl}-2-phenoxy- 2-yl)-acetamide ethanone and acytyl chloride245 (R)-N-(3-{5-[1-(2-Phenoxy- (R)-1-{2-[5-(3-Amino-phenyl)- 420.5acetyl)-piperidin-2-yl]-1H- 2H-[1,2,4]triazol-3-yl]-[1,2,4]triazol-3-yl}-phenyl)- piperidin-1-yl}-2-phenoxy- acetamideethanone and acytyl chloride 246 (R)-N-(3-{5-[1-(2-Phenoxy-(R)-1-{2-[3-(3-Amino-phenyl)- 457.4 acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl]-piperidin- [1,2,4]oxadiazol-3-yl}-phenyl)- 1yl}-2phenoxy-ethanone and methanesulfonamide mesyl chloride 247(R)-N-(4-{5-[1-(2-Phenoxy- (R)-1-{2-[3-(4-Amino-phenyl)- 457.4acetyl)-piperidin-2-yl]- [1,2,4]oxadiazol-5-yl]-piperidin-[1,2,4]oxadiazol-3-yl}-phenyl)- 1-yl}-2-phenoxy-ethanone andmethane-sulfonamide mesylchloride 248 (R)-(3-{5-[1-(2-Phenoxy-(R)-1-{2-[3-(3-Amino-phenyl)- 463.5 acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl]-piperidin- [1,2,4]oxadiazol-3-yl}-phenyl)- 1yl}-2phenoxy-ethanone acid carbamic acid allyl ester allyl ester 249(R)-(4-{5-[1-(2-Phenoxy- (R)-1-{2-[3-(4-Amino-phenyl)- 463.5acetyl)-piperidin-2-yl]- [1,2,4]oxadiazol-5-yl]-piperidin-[1,2,4]oxadiazol-3-yl}-phenyl)- 1-yl}-2-phenoxy-ethanone and carbamicacid allyl ester chloroformic acid allyl ester 250(R)-N-(3-{5-[1-(2-Phenoxy- (R)-1-{2-[5-(3-Amino-phenyl)- 456.5acetyl)-piperidin-2-yl]-1H- 2H-[1,2,4]triazol-3-yl]-[1,2,4]triazol-3-yl}-phenyl)- piperidin-1-yl}-2-phenoxy-methanesulfonamide ethanone and mesyl chloride 251(R)-1-Ethyl-3-(3-{5-[1-(2- (R)-1-{2-[5-(3-Amino-phenyl)- 449.5phenoxy-acetyl)-piperidin-2- 2H-[1,2,4]triazol-3-yl]-yl]-1H-[1,2,4]triazol-3-yl}- piperidin-1-yl}-2-phenoxy- phenyl)-ureaethanone and ethylisocyanate

Example 252(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzonitrile

1.3 mmol(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamidewere treated with neat trifluoroacetic anhydride at room temperatureovernight. The reaction was quenched with aqueous NaHCO₃ and productextracted with ethylacetate twice. The organic layers were washed withwater/NaCl, combined, dried over Na2SO4 and the solvent evaporated. Theproduct was purified via preparative HPLC.

MS(ISO): 388.5 (MH+)

Example 253(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinonitrile

0.15 mmol of5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamideare treated with trifluoracetic anhydride at room temperature overnight. The reaction was quenched with aqueous NaHCO₃ and productextracted with ethylacetate twice. The organic layers were washed withwater/NaCl, combined, dried over Na2SO4 and the solvent evaporated. Theproduct was purified via preparative HPLC.

MS(ISO): 390.4 (MH+)

Example 254 4-Acetyl-piperazine-1,2-dicarboxylic acid 1-tert-butyl ester

10 mmol of Piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methylester were dissolved in 20 ml methylenchloride. 1.05 eq of DIPEA andacetychloride were added. The reaction mixture was stirred at roomtemperature for 30 min. The product was extracted frometylacetate/water. The crude material was re-dissolved in methanol andtreated with 2N NaOH. The reaction mixture was stirred at roomtemperature for 2 h. The mixture was neutralized with HCl and theproduct isolated via extraction from ethylacetate/water.

MS(ISO): 271.3 (M−H+)

Example 255 4-Methanesulfonyl-piperazine-1,2-dicarboxylic acid1-tert-butyl ester

10 mmol of Piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methylester were dissolved in 20 ml methylenchloride. 1.05 eq of DIPEA andmesylchloride were added. The reaction mixture was stirred at roomtemperature for 30 min. The product was extracted frometylacetate/water. The crude material was redissolved in methanol andtreated with 2N NaOH. The reaction mixture was stirred at roomtemperature for 2 h. The mixture was neutralized with HCl and theproduct isolated via extraction from ethylacetate/water.

MS(ISO): 307.4 (M−H+)

Example 256 N-Hydroxy-4-sulfamoyl-benzamidine

1 mmol of 4-Cyano-benzenesulfonamide are dissolved in a mixture ofethanol/water (7:3) and 5 eq of hydroxylamine hydrochloride and 2.5 eq.Na2CO3 added. The suspension is heated to 80° C. for 2 h. Afterevaporation of the solvent mixture the resulting material is extractedfrom ethylacetate/water. The product was not further characterized.

MS(ISO): 216.3 (MH+)

All following compounds were prepared in analogy:

TABLE 7 Example Compound name Starting materials 2573-(N-Hydroxy-carbamimidoyl)- 3-Cyano-benzoic acid methyl ester benzoicacid methyl ester and hydroxylamine 258 4-(N-Hydroxycarbamimidoyl)-4-Cyano-pyridine-2-carboxylic acid pyridine-2-carboxylic acid ethylester ethyl ester 259 3-Fluoro-4-(N- 4-Cyano-3-fluoro-benzoic acidhydroxycarbamimidoyl)-benzoic acid methyl ester methyl ester 260N-Hydroxy-4-nitro-benzamidine 4-Nitro-benzonitrile and hydroxylamine 261N-Hydroxy-3-sulfamoyl-benzamidine 3-Cyano-benzenesulfonamide andhydroxylamine 262 N-Hydroxy-6-methoxy- 6-Methoxy-nicotinonitrile andnicotinamidine hydroxylamine 263 N-Hydroxy-3-hydroxymethyl-3-Hydroxymethyl-benzonitrile and benzamidine hydroxylamine 264N-Hydroxy-4-imidazol-1-yl- 4-Imidazol-1-yl-benzonitrile and benzamidinehydroxylamine 265 N-Hydroxy-6-morpholin-4-yl-6-Morpholin-4-yl-nicotinonitrile nicotinamidine and hydroxylamine 266N-Hydroxy-4- 4-Trifluoromethanesulfonyl- trifluoromethanesulfonyl-benzonitrile and hydroxylamine benzamidine 267N-Hydroxy-4-trifluoromethyl- 4-Trifluoromethyl-benzonitrile andbenzamidine hydroxylamine 268 4-Chloro-N-hydroxy-benzamidine4-Chloro-benzonitrile and hydroxylamine 269N-[4-(N-Hydroxycarbamimidoyl)-2- N-(4-Cyano-2-trifluoromethyl-trifluoromethyl-phenyl]-acetamide phenyl)-acetamide and hydroxylamine270 N-Hydroxy-3-methanesulfonyl- 3-Methanesulfonyl-benzonitrilebenzamidine and hydroxylamine 271 N-Hydroxy-4-methyl-3-nitro-4-Methyl-3-nitro-benzonitrile and benzamidine hydroxylamine 272N-Hydroxy-4-methoxy-3-nitro- 4-Methoxy-3-nitro-benzonitrile benzamidineand hydroxylamine 273 N-Hydroxy-2-oxo-1,2-dihydro-2-Oxo-1,2-dihydro-pyridine-4- pyridine-4-carboxamidine carbonitrile 274N-Hydroxy-6-oxo-1,6-dihydro- 6-Oxo-1,6-dihydro-pyridine-3-pyridine-3-carboxamidine carbonitrile 275N-Hydroxy-4-(1H-tetrazol-5-yl)- 4-(1H-Tetrazol-5-yl)-benzonitrilebenzamidine and hydroxylamine 276 N-Hydroxy-1H-indazole-5-1H-Indazole-5-carbonitrile and carboxamidine hydroxylamine 277N-Hydroxy-1H-indazole-6- 1H-Indazole-6-carbonitrile and carboxamidinehydroxylamine 278 4-Fluoro-N-hydroxy-3- 4-Fluoro-3-trifluoro-methyl-trifluoromethyl-benzamidine benzonitrile and hydroxylamine 279N-Hydroxy-2-oxo-2,3-dihydro-1H- 2-Oxo-2,3-dihydro-1H-indole-6-indole-6-carboxamidine carbonitrile and hydroxylamine 280N-Hydroxy-2-oxo-2,3-dihydro-1H- 2-Oxo-2,3-dihydro-1H-benzoimidazole-5-carboxamidine benzoimidazole-5-carbonitrile andhydroxylamine 281 N-Hydroxy-2-oxo-2,3-dihydro-1H-2-Oxo-2,3-dihydro-1H-indole-5- indole-5-carboxamidine carbonitrile andhydroxylamine 282 N-Hydroxy-pyridine-2- Pyridine-2-carbonitrile andcarboxamidine hydroxylamine 283 N-Hydroxy-pyridine-3-Pyridine-3-carbonitrile and carboxamidine hydroxylamine 2844-Diethylamino-N-hydroxy- 4-Diethylamino-benzonitrile and benzamidinehydroxylamine 285 N-[4-(N-Hydroxycarbamimidoyl)-2-N-(4-Cyano-2-trifluoromethyl- trifluoromethyl-phenyl]-acetamidephenyl)-acetamide and hydroxylamine 286 4-Chloro-N-hydroxy-3-nitro-4-Chloro-3-nitro-benzonitrile and benzamidine hydroxylamine 287N-Hydroxy-4-pyrrol-1yl- 4-Pyrrol-1-yl-benzonitrile and benzamidinehydroxylamine 288 2,4-Dichloro-N-hydroxy- 2,4-Dichloro-benzonitrile andbenzamidine hydroxylamine 289 N-Hydroxy-3-(2-oxo-piperidin-1-yl)-3-(2-Oxo-piperidin-1-yl)- benzamidine benzonitrile and hydroxylamine 290N-Hydroxy-1H-benzoimidazole-5- 1H-Benzoimidazole-5-carbonitrilecarboxamidine 291 6-(N-Hydroxy-carbamimidoyl)- 6-Cyano-nicotinic acidallyl ester nicotinic acid allyl ester and hydroxylamine 2924-(N-Hydroxycarbamimidoyl)- 4-Cyano-pyridine-2-carboxylic acidpyridine-2-carboxylic acid ethyl ester ethyl ester and hydroxylamine 2933-Fluoro-4-(N- 4-Cyano-3-fluoro-benzoic acidhydroxycarbamimidoyl)-benzoic acid methyl ester and bydroxylamine methylester 294 N-Hydroxy-1H-benzotriazole-5- 1H-Benzotriazole-5-carbonitrilecarboxamidine 294 6-Benzyloxy-N-hydroxy- 6-Benzyloxy-nicotinonitrilenicotinamidine 295 N-[5-(N-Hydroxycarbamimidoyl)-N-(5-Cyano-pyridin-2-yl)- pyridin-2-yl]-acetamide acetamide 296N-[4-(N-Hydroxycarbamimidoyl)- N-(4-Cyano-pyridin-2-yl)-pyridin-2-yl]-acetamide acetamide

Example 297 N-Hydroxy-4-methylsulfamoyl-benzamidine

5 mmol of 4-Cyano-benzenesulfonyl chloride were dissolved in 10 ml THF.10 ml of a 2M methylamine/THF solution was added dropwise. The reactionwas stirred at room temperature overnight. The solvent was evaporatedand the product extracted from ethylacetate/water. The nitril obtainedwas treated analogously to example 231.

MS(ISO): 230.5 (MH+)

All following compounds were prepared in analogy:

TABLE 8 Example Compound name Starting materials 298N-Hydroxy-4-(morpholine-4- 4-Cyano-benzenesulfonyl chloride andsulfonyl)-benzamidine morpholine 299 N-Hydroxy-4-(2-hydroxy-4-Cyano-benzenesulfonyl chloride ethylsulfamoyl)-benzamidine andethanolamine 300 N-Hydroxy-4-[(2-methoxy-ethyl)- 4-Cyano-benzenesulfonylchloride methyl-sulfamoyl]-benzamidine and (2-Methoxy-ethyl)-methylamine 301 4-Dimethylsulfamoyl-N-hydroxy- 4-Cyano-benzenesulfonylchloride benzamidine and dimethylamine 302 4-Diethylsulfamoyl-N-hydroxy-4-Cyano-benzenesulfonyl chloride benamidine and diethylamine

Example 303 6-(1,1-Dioxo-thiomorpholin-4-yl)-N-hydroxy-nicotinamidine

10 mmol of 6-Cl-4-CN-pyridine are dissolved in 10 ml DMF. 20 mmol ofmorpholine are added and the reaction heated to 120° C. under microwaveconditions for 20 min. The DMF is evaporated and the crude extractedfrom ethylacetate/water. After evaporation the resulting solid wastreated with 30 mmol of metha-chloroperbenzoic acid in DCM at roomtemperature overnight and the resulting precipitate filtered off andrecrystalized from MeOH. The nitril obtained was treated analogously toexample 231.

MS(ISO): 271.5 (MH+)

The following compounds were prepared in analogy.

TABLE 9 Example Compound name Starting materials 304N-Hydroxy-2-morpholin-4-yl- 2-Chloroisonicotinonitrile andisonicotinamidine morpholin 305 N-Hydroxy-3,4,5,6-tetrahydro-2-Chloroisonicotinonitrile and 2H-[1,2′]bipyridinyl-4′- piperidincarboxamidine 306 N-Hydroxy-2-thiomorpholin-4-yl-2-Chloroisonicotinonitrile and isonicotinamidine thiomorpholin 3072-Diethylamino-N-hydroxy- 2-Chloroisonicotinonitrile andisonicotinamidine diethylamine 308 N-Hydroxy-6-(3-oxo-piperazin-1-2-Chloronicotinonitrile and Piperazin- yl)-nicotinamidine 2-one 3096-(4-Acetyl-piperazin-1-yl)-N- 2-Chloronicotinonitrile and 1-hydroxy-nicotinamidine acetylpiperazin 310 N-Hydroxy-6-(3-hydroxymethyl-2-Chloronicotinonitrile and Pyrrolidin- pyrrolidin-1-yl)-nicotinamidine3-yl-methanol 311 N-Hydroxy-6-morpholin-4-yl- 2-Chloronicotinonitrileand morpholin nicotinamidine

Example 312 4-Fluoro-N-amino-benzamidine hydrochloride

82 mmol of 3-Cyano-benzoic acid methyl ester were dissolved in 50 m1 ofan HCl-saturated methylenchloride solution and 50 ml of methanol. Underice-bath cooling HCl-gas was bubbled through the solution to keep thetemperature under 20° C. The reaction mixture was stirred overnight atroom temperature. lOOml of diethylether were added and the resultingsolid filtered off, washed with diethylether and dried under vaccum. Theresulting imidoether was extracted from ethylacetate/aq.sodiumbicarbonate to result in an oily residue. This was taken up in 25ml methanol and treated with 1 ml hydrazin monohydrate at roomtemperature overnight. The solution was slowly added to a cold solutionof 4N HCl/dioxan. 80 ml of diethylether were added and the suspensionstirred at room temperature for 30 min. The solid was filtered off andwashed with diethylether and dried under vacuum. The product wasconfirmed by MS.

MS(ISO): 194.4 (MH+)

The following compounds were prepared in analogy:

TABLE 10 Example Compound name Starting materials 3134-Fluoro-N-amino-3- 4-Fluoro-3-trifluoromethyl-trifluoromethyl-benzamidine benzonitrile and hydrazine hydrochloride 314N-Amino-4-methanesulfonyl- 4-Methanesulfonyl-benzonitril and benzamidinehydrochloride hydrazine 315 N-Amino-3-trifluoromethyl-m-Trifluoromethyl-benzonitril and hydrazine benzamidine hydrochloride316 N-Amino-4-methyl-benzamidine p-Tolunitril and hydrazinehydrochloride 317 N-Amino-4-trifluoromethyl-p-Trifluoromethyl-benzonitril and benzamidine hydrochloride hydrazine318 N-Amino-4-methoxy-benzamidine 4-Methoxybenzonitrile andhydrochloride hydrazine 319 N-Amino-2,4-difluoro-benzamidine2,4-Difluorobenzonitrile and hydrochloride hydrazine 320N-Amino-3,4-dimethoxy- 3,4-Dimethoxybenzonitrile and benzamidinehydrochloride hydrazine 321 N-Amino-3,4-dichloro-benzamidine3,4-Dichlorobenzonitrile and hydrochloride hydrazine 322N-Amino-benzamidine hydrochloride Benzonitrile and hydrazine 323N-Amino-3-Nitro-benzamidine 3-Nitrobenzonitrile and hydrazinehydrochloride 324 N-Amino-3-methylester-benzamidine 3-Cyano-benzoic acidmethyl ester hydrochloride and hydrazine 325N-Amino-2-oxo-2,3-dihydro-1H- 2-Oxo-2,3-dihydro-1H-indole-6-indole-6-carboxamidine carbonitrile and hydrazine 326N-Amino-2-fluoro-benzamidine 2-Fluorobenzonitrile and hydrazinehydrochloride

Example 327 6-Cyano-nicotinic acid allyl ester

4 mmol of 6-Cyanonicotinic acid were dissolved in THF. 1.5 eq. of Cs2CO3were added he reaction stirred for 10 min. 1.5 eq allylbromide and acatalytic amount of KI were added he reaction heated to 100° C. for 4 h.The product was isolated via extraction from cetate/water.

MS(ISO): 222.5 (MH+)

Example 328 1H-Benzotriazole-5-carbonitrile

10 mmol of 3,4-Diamino-benzonitrile were suspended in water/acetic acid(4:1) and cooled to 0° C. 1.05 eq of NaNO2 were dissolved in water andadded inert 30 min. The reaction was stirred at room temperatureovernight. The precipitate was filtered off, washed with ether and driedunder vacuum. The intermediate was not further characterized.

Example 329 6-Benzyloxy-nicotinonitrile

20 mmol of 6-Chloro-nicotinonitrile were dissolved in THF. 1.1 eq. ofbenzyl alcohol were added. The reaction mixture was cooled to 0° C. andflushed with argon. 4 eq of NaH were added slowly. After 15 min theproduct was isolated via extraction from ethylacetate/water.

MS(ISO): 211.5 (MH+)

Example 330 N-(5-Cyano-pyridin-2-yl)-acetamide

8 mmol of 6-Amino-nicotinonitrile were dissolved in THF. 2 eq of DIPEAwere added. The reaction mixture was cooled to 0° C. and 1.0 eq ofacetylchloride in THF added dropwise and the reaction stirred for 2 h.The product was isolated by extraction from ethylacetate/water.

MS(ISO): 162.2 (MH+)

Example 331 N-(4-Cyano-pyridin-2-yl)-acetamide

8 mmol of 2-Amino-isonicotinonitrile were dissolved in THF. 2 eq ofDIPEA were added. The reaction mixture was cooled to 0° C. and 1.0 eq ofacetylchloride in THF added dropwise and the reaction stirred for 2 h.The product was isolated by extraction from ethylacetate/water.

MS(ISO): 162.2 (MH+)

The following compounds were generated in analogy to example 1

MH+ Example Compound name Starting materials (found) 3321-{2-[3-(2-Methyl-1H- Boc-D-Pipecolic Acid, N- 418.5benzoimidazol-5-yl)- Hydroxy-2-methyl-1H- [1,2,4]oxadiazol-5-yl]-benzoimidazole-5- piperidin-1-yl}-2-phenoxy- carboxamidine and ethanonephenoxyacetyl chloride 333 1-{2-[3-(2-Amino-pyridin-4- Boc-D-PipecolicAcid, 2- 380.5 yl)-[1,2,4]oxadiazol-5-yl]- Amino-N-hydroxy-piperidin-1-yl}-2-phenoxy- isonicotinamidine and ethanone phenoxyaceticacid 334 1-{2-[3-(3-Hydroxy-phenyl)- Boc-D-Pipecolic Acid, 3-N- 380.5[1,2,4]oxadiazol-5-yl]- Dihydroxy-benzamidine andpiperidin-1-yl}-2-phenoxy- phenoxyacetic acid ethanone 3354-{5-[1-(2-Phenoxy-acetyl)- Boc-D-Pipecolic Acid, 2,N- 381.4piperidin-2-yl]- Dihydroxy-isonicotinamidine [1,2,4]oxadiazol-3-yl}-1H-and phenoxyacetyl chloride pyridin-2-one 336 1-{2-[3-(4-Hydroxy-phenyl)-Boc-D-Pipecolic Acid, 4-N- 379.6 [1,2,4]oxadiazol-5-yl]-Dihydroxy-benzamidine and piperidin-1-yl}-2-phenoxy- phenoxyacetic acidethanone 337 3-{5-[1-(2-Phenoxy-acetyl)- Boc-D-Pipecolic Acid, 3-(N-407.7 piperidin-2-yl]- Hydroxycarbamidoyl)- [1,2,4]oxadiazol-3-yl}-phenylboronic acid and phenylboronic acid phenoxyacetyl chloride 3384-(2-Oxo-2-{2-[3-(2-oxo-2,3- Boc-D-Pipecolic Acid, N- 443.7dihydro-1H-indol-5-yl)- Hydroxy-2-oxo-2,3-dihydro-[1,2,4]oxadiazol-5-yl]- 1H-indole-5-carboxamidinepiperidin-1-yl}-ethoxy)- and 4-cyanophenoxyacetic acid benzonitrile 3394-(2-{2-[3-(4-Methoxy- Boc-D-Pipecolic Acid, N- 419.3phenyl)-[1,2,4]oxadiazol-5-yl]- Hydroxy-4-methoxy-piperidin-1-yl}-2-oxo-ethoxy)- benzamidine and 4- benzonitrilecyanophenoxyacetic acid 340 2-Methyl-5-{5-[1-(2-phenoxy- Boc-D-PipecolicAcid, 4,N- 396.2 acetyl)-piperidin-2-yl]- Dihydroxy-2-methyl-[1,2,4]oxadiazol-3-yl}-3H- pyrimidine-5-carboxamidine pyrimidin-4-oneand phenoxyacetyl chloride 341 1-[(R)-2-(3-Furan-2-yl- Boc-D-PipecolicAcid, N- 354.2 [1,2,4]oxadiazol-5-yl)- Hydroxy-furan-2-piperidin-1-yl]-2-phenoxy- carboxamidine and ethanone phenoxyacetylchloride 342 1-[(R)-2-(3-Imidazo[1,2- Boc-D-Pipecolic Acid, N- 404.2a]pyridin-2-yl- Hydroxy-imidazo[1,2- [1,2,4]oxadiazol-5-yl)-a]pyridine-2-carboxamidine piperidin-1-yl]-2-phenoxy- and phenoxyacetylchloride ethanone 343 1-{(R)-2-[3-(4-Methyl- Boc-D-Pipecolic Acid, N-386.2 [1,2,3]thiadiazol-5-yl)- Hydroxy-4-methyl- [1,2,4]oxadiazol-5-yl]-[1,2,3]thiadiazole-5- piperidin-1-yl}-2-phenoxy- carboxamidine andethanone phenoxyacetyl chloride 344 1-{(R)-2-[3-(2,5-Dimethyl-Boc-D-Pipecolic Acid, N- 382.2 2H-pyrazol-3-yl)-Hydroxy-2,5-dimethyl-2H- [1,2,4]oxadiazol-5-yl]-pyrazole-3-carboxamidine and piperidin-1-yl}-2-phenoxy- phenoxyacetylchloride ethanone 345 2-Phenoxy-1-{(R)-2-[3-(1H- Boc-D-Pipecolic Acid,N- 354.2 pyrazol-4-yl)-[1,2,4]oxadiazol- Hydroxy-1H-pyrazole-4-5-yl]-piperidin-1-yl}-ethanone carboxamidine and phenoxyacetyl chloride346 1-{(R)-2-[3-(5-Methyl- Boc-D-Pipecolic Acid, N- 369.2isoxazol-3-yl)- Hydroxy-5-methyl-isoxazole-3- [1,2,4]oxadiazol-5-yl]-carboxamidine and piperidin-1-yl}-2-phenoxy- phenoxyacetyl chlorideethanone 347 2-Phenoxy-1-{(R)-2-[3-(1H- Boc-D-Pipecolic Acid, N- 354.2pyrazol-3-yl)-[1,2,4]oxadiazol- Hydroxy-1H-pyrazole-3-5-yl]-piperidin-1-yl}-ethanone carboxamidine and phenoxyacetyl chloride348 5-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, 2,4,N- 398.2acetyl)-piperidin-2-yl]- Trihydroxy-pyrimidine-5-[1,2,4]oxadiazol-3-yl}-1H- carboxamidine and pyrimidine-2,4-dionephenoxyacetyl chloride 349 1-{(R)-2-[3-(6-Amino- Boc-D-Pipecolic Acid,6- 380.5 pyridin-3-yl)-[1,2,4]oxadiazol- Amino-N-hydroxy5-yl]-piperidin-1-yl}-2- nicotinamidine and phenoxy-ethanonephenoxyacetyl chloride 350 1-[(R)-2-(3-Imidazo[1,2- Boc-D-PipecolicAcid, N- 404.2 a]pyridin-6-yl- Hydroxy-imidazo[1,2-[1,2,4]oxadiazol-5-yl)- a]pyridine-6-carboxamidinepiperidin-1-yl]-2-phenoxy- and phenoxyacetyl chloride ethanone 3516-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 435.2acetyl)-piperidin-2-yl]- Hydroxy-3-oxo-3,4-dihydro-[1,2,4]oxadiazol-3-yl}-4H- 2H-benzo[1,4]oxazine-6-benzo[1,4]oxazin-3-one carboxamidine and phenoxyacetyl chloride 3526-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 435.2acetyl)-piperidin-2-yl]- Hydroxy-2-oxo-1,4-dihydro-[1,2,4]oxadiazol-3-yl}-1,4- 2H-benzo[d][1,3]oxazine-6-dihydro-benzo[d][1,3]oxazin- carboxamidine and 2 one phenoxyacetylchloride 353 1-((R)-2-{3-[3-(1,1-Dioxo- Boc-D-Pipecolic Acid, 3-(1,1-483.3 1$$6-isothiazolidin-2-yl)- Dioxo-1$$6-isothiazolidin-2-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}- N-hydroxy-benzamidine andpiperidin-1-yl)-2-phenoxy- phenoxyacetyl chloride ethanone 3541-(3-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 447.3acetyl)-piperidin-2-yl]- Hydroxy-3-(2-oxo-pyrrolidin-[1,2,4]oxadiazol-3-yl}-phenyl)- 1-yl)-benzamidine and pyrrolidin-2-onephenoxyacetyl chloride 355 1-(3-{5-[(R)-1-(2-Phenoxy- Boc-D-PipecolicAcid, 3-(2,4- 462.5 acetyl)-piperidin-2-yl]- Dioxo-imidazolidin-1-yl)-N-[1,2,4]oxadiazol-3-yl}-phenyl)- hydroxy-benzamidine andimidazolidine-2,4-dione phenoxyacetyl chloride 3564-(3-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 447.5acetyl)-piperidin-2-yl]- Hydroxy-3-(5-oxo-1,5-dihydro-[1,2,4]oxadiazol-3-yl}-phenyl)- [1,2,4]triazol-4-yl)-benzamidine2,4-dihydro-[1,2,4]triazol-3- and phenoxyacetyl chloride one 3571-(3-Fluoro-5-{5-[(R)-1-(2- Boc-D-Pipecolic Acid, 3-(2,5- 479.2phenoxy-acetyl)-piperidin-2- Dioxo-pyrrolidin-1-yl)-5-yl]-[1,2,4]oxadiazol-3-yl}- fluoro-N-hydroxy-benzamidinephenyl)-pyrrolidine-2,5-dione and phenoxyacetyl chloride 3585-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 418.5acetyl)-piperidin-2-yl]-1H- Amino-2-Oxo-2,3-dihydro-1H-[1,2,4]triazol-3-yl}-1,3- indole-5-carboxamidine and dihydro-indol-2-onephenoxyacetic acid 359 1-{(R)-2-[5-(1H-Indazol-5- Boc-D-Pipecolic Acid,N- 403.5 yl)-2H-[1,2,4]triazol-3-yl]- Amino-1H-Indazole-5-piperidin-1-yl}-2-phenoxy- carboxamidine and ethanone phenoxyacetic acid360 1-{(R)-2-[5-(1H-Indol-5-yl)- Boc-D-Pipecolic Acid, N- 402.52H-[1,2,4]triazol-3-yl]- Amino-1H-Indole-5- piperidin-1-yl}-2-phenoxy-carboxamidine and ethanone phenoxyacetic acid 3611-{(R)-2-[5-(3H-Benzotriazol- Boc-D-Pipecolic Acid, N- 402.5(M − H+)5-yl)-2H-[1,2,4]triazol-3-yl]- Amino-3H-Benzotriazole-5-piperidin-1-yl}-2-phenoxy- carboxamidine and ethanone phenoxyacetic acid362 5-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 419.5acetyl)-piperidin-2-yl]-1H- Amino-2-Oxo-2,3-dihydro-1H-[1,2,4]triazol-3-yl}-1,3- benzoimidazole-5- dihydro-benzoimidazol-2-onecarboxamidine and phenoxyacetic acid 363 1-{(R)-2-[5-(2-Methyl-1H-Boc-D-Pipecolic Acid, N- 417.5 benzoimidazol-5-yl)-2H-Amino-2-Methyl-1H- [1,2,4]triazol-3-yl]-piperidin- benzoimidazole-5-1-yl}-2-phenoxy-ethanone carboxamidine and phenoxyacetic acid 3641-{(R)-2-[5-(2-Amino- Boc-D-Pipecolic Acid, N- 379.5 pyridin-4-yl)-2H-Amino-2-Amino- [1,2,4]triazol-3-yl]-piperidin- isonicotinamidine and1-yl}-2-phenoxy-ethanone phenoxyacetic acid 3655-(3-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, N- 446.7acetyl)-piperidin-2-yl]-1H- Amino-3-(5-Oxo-4,5-dihydro-[1,2,4]triazol-3-yl}-phenyl)- [1,3,4]oxadiazol-2-yl)-3H-[1,3,4]oxadiazol-2-one benzamidine and phenoxyacetic acid 3661-{(R)-2-[5-(3- Boc-D-Pipecolic Acid, N- 430.7[1,3,4]Oxadiazol-2-yl-phenyl)- Amino-3-[1,3,4]Oxadiazol-2-yl-2H-[1,2,4]triazol-3-yl]- benzamidine and phenoxyaceticpiperidin-1-yl}-2-phenoxy- acid ethanone 367 3-{5-[1-(2-Phenoxy-acetyl)-Boc-D-Pipecolic Acid, N- 407.5 piperidin-2-yl]-1H- Amino-3-Carbamidoyl-[1,2,4]triazol-3-yl}- phenylboronic acid and phenylboronic acidphenoxyacetic acid

Example 3686-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-4H-benzo[1,4]oxazin-3-one

Step 1:

2-Hydrazinocarbonyl-piperidine-1-carboxylic acid tert-butyl ester

3 g of (R)-Piperidine-1,2-dicarboxylic acid 1-tert-butyl ester weredissolved in 30 ml DMF. 5 g HATU and 2.2 ml DIPEA were added and thereaction mixture cooled to 0° C. 4 eq. of Hydrazine-Monohydrate in 30 mlDMF were added and the reaction warmed to rt and stirred for 1 h. Thecrude product was extracted from ethylacetate/aq. NaHCO3.

MS(ISO): 244.3 (MH+)

Step 2:

6-(5-Piperidin-2-yl-1H-[1,2,4]triazol-3-yl)-4H-benzo[1,4]oxazin-3-one

1.5 mmol of 2-Hydrazinocarbonyl-piperidine-1-carboxylic acid tert-butylester were dissolved in 3 ml DMF. 1 eq of3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxamidine and 90 ul aceticacid were added and the reaction mixture heated to 120° C. overnight.The solvent was evaporated and the crude extracted fromethylacetate/water. The resulting oil was taken up in 15 ml DCM andtreated with 3 ml TFA. The reaction mixture was reduced to dryness.

Step 3:

6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-4H-benzo[1,4]oxazin-3-one

Crude product from step 3 was taken up in DMF and cooled to 0° C. 4 eq.DIPEA and 1 eq of phenoxyacetyl chloride were added dropwise and thereaction mixture warmed to rt and stirred for additional 30 min. Theproduct was isolated via preparative HPLC.

The following compounds were generated in analogy to example 368

MH+ Example Compound name Starting materials (found) 3691-[(R)-2-(5-Imidazo[1,2- Boc-D-Pipecolic Acid, 443.7 a]pyridin-6-yl-2H-Imidazo[1,2-a]pyridine-6- [1,2,4]triazol-3-yl)-piperidin- carboxamidineand 1-yl]-2-phenoxy-ethanone phenoxyacetic acid 3701-{(R)-2-[5-(6-Amino- Boc-D-Pipecolic Acid, 6- 379.1 pyridin-3-yl)-2H-Amino-nicotinamidineand [1,2,4]triazol-3-yl]-piperidin- phenoxyaceticacid 1-yl}-2-phenoxy-ethanone 371 1-{(R)-2-[5-(1H- Boc-D-Pipecolic Acid,1H- 403.2 Benzoimidazol-5-yl)-2H- Benzoimidazole-5-[1,2,4]triazol-3-yl]-piperidin- carboxamidine and1-yl}-2-phenoxy-ethanone phenoxyacetic acid 372 2-Phenoxy-1-[(R)-2-(5-Boc-D-Pipecolic Acid, 364.2 pyridin-3-yl-2H-[1,2,4]triazol-Nicotinamidine and 3-yl)-piperidin-1-yl]-ethanone phenoxyacetic acid 3731-{(R)-2-[5-(3,5-Dimethyl- Boc-D-Pipecolic Acid, 3,5- 382.2isoxazol-4-yl)-2H- Dimethyl-isoxazole-4- [1,2,4]triazol-3-yl]-piperidin-carboxamidine and 1-yl}-2-phenoxy-ethanone phenoxyacetic acid 3742-Phenoxy-1-[(R)-2-(5- Boc-D-Pipecolic Acid, 369.1 thiophen-2-yl-2H-Thiophene-2-carboxamidine [1,2,4]triazol-3-yl)-piperidin- andphenoxyacetic acid 1-yl]-ethanone 375 2-Phenoxy-1-[(R)-2-(5-Boc-D-Pipecolic Acid, 365.1 pyrimidin-2-yl-2H-Pyrimidine-2-carboxamidine [1,2,4]triazol-3-yl)-piperidin- andphenoxyacetic acid 1-yl]-ethanone 376 1-{(R)-2-[5-(4-Methyl-oxazol-Boc-D-Pipecolic Acid, 4- 368.1 5-yl)-2H-[1,2,4]triazol-3-yl]-Methyl-oxazole-5- piperidin-1-yl}-2-phenoxy- carboxamidine and ethanonephenoxyacetic acid 377 2-Phenoxy-1-[(R)-2-(5- Boc-D-Pipecolic Acid,Pyrazine- 365.1 pyrazin-2-yl-2H-[1,2,4]triazol- 2-carboxamidine and3-yl)-piperidin-1-yl]-ethanone phenoxyacetic acid 3781-{(R)-2-[5-(2-Fluoro- Boc-D-Pipecolic Acid, 2- 381.1phenyl)-2H-[1,2,4]triazol-3- Fluoro-benzamidine andyl]-piperidin-1-yl}-2-phenoxy- phenoxyacetic acid ethanone 3791-{(R)-2-[5-(3,5-Difluoro- Boc-D-Pipecolic Acid, 3,5- 399.1phenyl)-2H-[1,2,4]triazol-3- Difluoro-benzamidine andyl]-piperidin-1-yl}-2-phenoxy- phenoxyacetic acid ethanone 3801-{(R)-2-[5-(2-Methyl- Boc-D-Pipecolic Acid, 2- 378.1 pyridin-4-yl)-2H-Methyl-isonicotinamidine and [1,2,4]triazol-3-yl]-piperidin-phenoxyacetic acid 1-yl}-2-phenoxy-ethanone 381 1-{(R)-2-[5-(3-Fluoro-Boc-D-Pipecolic Acid, 3- 381.1 phenyl)-2H-[1,2,4]triazol-3-Fluoro-benzamidine and yl]-piperidin-1-yl}-2-phenoxy- phenoxyacetic acidethanone 382 1-{(R)-2-[5-(3,4-Difluoro- Boc-D-Pipecolic Acid, 3,4- 399.1phenyl)-2H-[1,2,4]triazol-3- Difluoro-benzamidine andyl]-piperidin-1-yl}-2-phenoxy- phenoxyacetic acid ethanone 3836-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, 2-Oxo- 434.5acetyl)-piperidin-2-yl]-1H- 1,4-dihydro-2H- [1,2,4]triazol-3-yl}-1,4-benzo[d][1,3]oxazine-6- dihydro-benzo[d][1,3]oxazin- carboxamidine and2-one phenoxyacetic acid 384 7-{5-[(R)-1-(2-Phenoxy- Boc-D-PipecolicAcid, 2-Oxo- 433.5 acetyl)-piperidin-2-yl]-1H-1,2,3,4-tetrahydro-quinazoline- [1,2,4]triazol-3-yl}-3,4-7-carboxamidine and dihydro-1H-quinazolin-2-one phenoxyacetic acid 3851-(3-{5-[(R)-1-(2-Phenoxy- Boc-D-Pipecolic Acid, 3-(2,4- 461.3acetyl)-piperidin-2-yl]-1H- Dioxo-imidazolidin-1-yl)-[1,2,4]triazol-3-yl}-phenyl)- benzamidine and phenoxyaceticimidazolidine-2,4-dione acid

The following compounds were generated in analogy to example 1

MH+ Example Compound name Starting materials (found) 3861-{(R)-3-[3-(2-Amino- (R)-Morpholine-3,4- 381.6pyridin-4-yl)-[1,2,4]oxadiazol- dicarboxylic acid 4-tert-butyl5-yl]-morpholin-4-yl}-2- ester, 2-Amino-N-hydroxy- phenoxy-ethanoneisonicotinamidine and phenoxyacetyl chloride 387 1-{(R)-3-[3-(1H-(R)-Morpholine-3,4 406.2 Benzoimidazol-5-yl)- dicarboxylic acid4-tert-butyl [1,2,4]oxadiazol-5-yl]- ester, N-Hydroxy-1H-morpholin-4-yl}-2-phenoxy- benzoimidazole-5- ethanone carboxamidine andphenoxyacetyl chloride 388 1-{(R)-2-[3-(1H- Piperazine-1,3-dicarboxylicacid 405.4 Benzoimidazol-5-yl)- 1-tert-butyl ester, N-Hydroxy-[1,2,4]oxadiazol-5-yl]- 1H-benzoimidazole-5- piperazin-1-yl}-2-phenoxy-carboxamidine and ethanone phenoxyacetic acid 3895-{5-[(R)-1-(2-Phenoxy- Piperazine-1,3-dicarboxylic acid 420.4acetyl)-piperazin-2-yl]- 1-tert-butyl ester, N-Hydroxy-[1,2,4]oxadiazol-3-yl}-1,3- 2-oxo-2,3-dihydro-1H-indole-dihydro-indol-2-one 5-carboxamidine and phenoxyacetic acid 3901-{(R)-2-[3-(2-Amino- Piperazine-1,3-dicarboxylic acid 380.6pyridin-4-yl)-[1,2,4]oxadiazol- 1-tert-butyl ester, 2-Amino-N-5-yl]-piperazin-1-yl}-2- hydroxy-isonicotinamidine and phenoxy-ethanonephenoxyacetic acid

Example 391(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenoxy)-aceticacid

The title compound was prepared in analogy to example 180 from(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenoxy)-aceticacid methylester. MS: 436.5 (M−H+)

The following compounds were generated in analogy to example 194

MH+ Example Compound name Starting materials (found) 3922-Phenoxy-1-((R)-2-{5-[3- 3-{5-[1-(2-Phenoxy-acetyl)- 474.6(piperidine-1-carbonyl)- piperidin-2-yl]-1H-phenyl]-2H-[1,2,4]triazol-3- [1,2,4]triazol-3-yl}-benzoic acidyl}-piperidin-1-yl)-ethanone and piperidine 3931-((R)-2-{5-[3-(Morpholine-4- 3-{5-[1-(2-Phenoxy-acetyl)- 476.6carbonyl)-phenyl]-2H- piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-piperidin- [1,2,4]triazol-3-yl}-benzoic acid1-yl)-2-phenoxy-ethanone and morpholine 394 1-((R-2-{5-[3-(4-Methyl-3-{5-[1-(2-Phenoxy-acetyl)- 489.7 piperazine-1-carbonyl)-piperidin-2-yl]-1H- phenyl]-2H-[1,2,4]triazol-3-[1,2,4]triazol-3-yl}-benzoic acid yl}-piperidin-1-yl)-2-phenoxy- andN-methylpiperazine ethanone 395 4-(3-{5-[(R)-1-(2-Phenoxy-3-{5-[1-(2-Phenoxy-acetyl)- 489.6 acetyl)-piperidin-2-yl]-1H-piperidin-2-yl]-1H- [1,2,4]triazol-3-yl}-benzoyl)-[1,2,4]triazol-3-yl}-benzoic acid piperazin-2-one and Piperazin-2-one396 N-(2-Methoxy-ethyl)-N- 3-{5-[1-(2-Phenoxy-acetyl)- 478.6methyl-3-{5-[(R)-1-(2- piperidin-2-yl]-1H- phenoxy-acetyl)-piperidin-2-[1,2,4]triazol-3-yl}-benzoic acid yl]-1H-[1,2,4]triazol-3-yl}- and(2-Methoxy-ethyl)-methyl- benzamide amine 397 1-((R)-2-{5-[3-(4-Acetyl-3-{5-[1-(2-Phenoxy-acetyl)- 517.7 piperazine-1-carbonyl)-piperidin-2-yl]-1H- phenyl]-2H-[1,2,4]triazol-3-[1,2,4]triazol-3-yl}-benzoic acid yl}-piperidin-1-yl)-2-phenoxy- and1-Piperazin-1-yl-ethanone ethanone 398 1-(3-{5-[(R)-1-(2-Phenoxy-3-{5-[1-(2-Phenoxy-acetyl)- 518.6 acetyl)-piperidin-2-yl]-1H-piperidin-2-yl]-1H [1,2,4]triazol-3-yl}-benzoyl)-[1,2,4]triazol-3-yl}-benzoic acid piperidine-4-carboxylic acid andPiperidine-4-carboxylic acid 399 1-(3-{5-[(R)-1-(2-Phenoxy-3-{5-[1-(2-Phenoxy-acetyl)- 517.7 acetyl)-piperidin-2-yl]-1H-piperidin-2-yl]-1H- [1,2,4]triazol-3-yl}-benzoyl)-[1,2,4]triazol-3-yl}-benzoic acid piperidine-4-carboxylic acid andPiperidine-4-carboxylic amide acid amide 400 2-Phenoxy-1-((R)-2-{5-[3-3-{5-[1-(2-Phenoxy-acetyl)- 478.6 (thiazolidine-3-carbonyl)-piperidin-2-yl]-1H- phenyl]-2H-[1,2,4]triazol-3-[1,2,4]triazol-3-yl}-benzoic acid yl}-piperidin-1-yl)-ethanone andThiazolidine 401 N-(2-Dimethylamino-ethyl)- 3-{5-[1-(2-Phenoxy-acetyl)-491.7 N-methyl-3-{5-[(R)-1-(2- piperidin-2-yl]-1H-phenoxy-acetyl)-piperidin-2- [1,2,4]triazol-3-yl}-benzoic acidyl]-1H-[1,2,4]triazol-3-yl}- and N,N,N′-Trimethyl-ethane- benzamide1,2-diamine 402 2-Phenoxy-1-((R)-2-{5-[3- 3-{5-[1-(2-Phenoxy-acetyl)-492.8 (thiomorpholine-4-carbonyl)- piperidin-2-yl]-1H-phenyl]-2H-[1,2,4]triazol-3- [1,2,4]triazol-3-yl}-benzoic acidyl}-piperidin-1-yl)-ethanone and thiomorpholine 4034-(3-{5-[(R)-1-(2-Phenoxy- 3-{5-[1-(2-Phenoxy-acetyl)- 547.7acetyl)-piperidin-2-yl]-1H- piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)- [1,2,4]triazol-3-yl}-benzoic acidpiperazine-1-carboxylic acid and Piperazine-1-carboxylic ethyl esteracid ethyl ester 404 N-(2-Hydroxy-ethyl)-3-{5-3-{5-[1-(2-Phenoxy-acetyl)- 450.6 [(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H- piperidin-2-yl]-1H- [1,2,4]triazol-3-yl}-benzoicacid [1,2,4]triazol-3-yl}-benzamide and aminoethanol 405N-Methyl-3-{5-[(R)-1-(2- 3-{5-[1-(2-Phenoxy-acetyl)- 525.7phenoxy-acetyl)-piperidin-2- piperidin-2-yl]-1H-yl]-1H-[1,2,4]triazol-3-yl}-N- [1,2,4]triazol-3-yl}-benzoic acid(2-pyridin-2-yl-ethyl)- and Methyl-(2-pyridin-2-yl- benzamideethyl)-amine 406 N-(2-Cyano-ethyl)-N- 3-{5-[1-(2-Phenoxy-acetyl)- 499.6cyclopropyl-3-{5-[(R)-1-(2- piperidin-2-yl]-1H-phenoxy-acetyl)-piperidin-2- [1,2,4]triazol-3-yl}-benzoic acidyl]-1H-[1,2,4]triazol-3-yl}- and 3-Cyclopropylamino- benzamidepropionitrile 407 1-(3-{5-[(R)-1-(2-Phenoxy- 3-{5-[1-(2-Phenoxy-acetyl)-575.7 acetyl)-piperidin-2-yl]-1H- piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-4- [1,2,4]triazol-3-yl}-benzoic acidphenyl-piperidine-4- and 4-Phenyl-piperidine-4- carbonitrilecarbonitrile 408 1-((R)-2-{5-[3-(4-Hydroxy- 3-{5-[1-(2-Phenoxy-acetyl)-490.6 piperidine-1-carbonyl)- piperidin-2-yl]-1H-phenyl]-2H-[1,2,4]triazol-3- [1,2,4]triazol-3-yl}-benzoic acidyl}-piperidin-1-yl)-2-phenoxy- and Piperidin-4-ol ethanone 4098-(3-{5-[(R)-1-(2-Phenoxy- 3-{5-[1-(2-Phenoxy-acetyl)- 558.6acetyl)-piperidin-2-yl]-1H- piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)- [1,2,4]triazol-3-yl}-benzoic acid1,3,8-triaza-spiro[4.5]decane- and 1,3,8-Triaza- 2,4-dionespiro[4.5]decane-2,4-dione 410 1-(2-{5-[3-(Spiro(1-Phtalan)-3-{5-[1-(2-Phenoxy-acetyl)- 578.7 piperidine-4-carbonyl)-piperidin-2-yl]-1H- phenyl]-2H-[1,2,4]triazol-3-[1,2,4]triazol-3-yl}-benzoic acid yl}-piperidin-1-yl)-2-phenoxy- and4-Spiro(1-Phtalan)- ethanone piperidine 411 2-Phenoxy-1-((R)-2-{5-[3-(3-3-{5-[1-(2-Phenoxy-acetyl)- 537.7 pyridin-4-yl-pyrrolidine-1-piperidin-2-yl]-1H- carbonyl)-phenyl]-2H- [1,2,4]triazol-3-yl}-benzoicacid [1,2,4]triazol-3-yl}-piperidin- and 4-Pyrrolidin-3-yl-pyridine1-yl)-ethanone 412 1-((R)-2-{5-[3-(3- 3-{5-[1-(2-Phenoxy-acetyl)- 538.6Methanesulfonyl-pyrrolidine- piperidin-2-yl]-1H- 1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-benzoic acid [1,2,4]triazol-3-yl}-piperidin- and3-Methanesulfonyl- 1-yl)-2-phenoxy-ethanone pyrrolidine 4131-((R)-2-{5-[3-((S)-3-Ethoxy- 3-{5-[1-(2-Phenoxy-acetyl)- 504.6pyrrolidine-1-carbonyl)- piperidin-2-yl]-1H-phenyl]-2H-[1,2,4]triazol-3- [1,2,4]triazol-3-yl}-benzoic acidyl}-piperidin-1-yl)-2-phenoxy- and (S)-3-Ethoxy-pyrrolidine ethanone 4141-((R)-2-{5-[3-((S)-3- 3-{5-[1-(2-Phenoxy-acetyl)- 476.6Hydroxy-pyrrolidine-1- piperidin-2-yl]-1H- carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-benzoic acid [1,2,4]triazol-3-yl}-piperidin- and(S)-3-Hydroxy-pyrrolidine 1-yl)-2-phenoxy-ethanone

The following compounds were generated according to example 231

MH+ Example Compound name Starting materials (found) 4155-{5-[(R)-1-(2-Phenoxy- 5-{5-[1-(2-Phenoxy-acetyl)- 407.5acetyl)-piperidin-2-yl]-1H- piperidin-2-yl]-1H- [1,2,4]triazol-3-yl}-[1,2,4]triazol-3-yl}-nicotinic nicotinamide acid and Rink resin 4162-(3-{5-[1-(2-Phenoxy-acetyl)- (3-{5-[1-(2-Phenoxy-acetyl)- 437.5piperidin-2-yl]- piperidin-2-yl]- [1,2,4]oxadiazol-3-yl}-[1,2,4]oxadiazol-3-yl}- phenoxy)-acetamide phenoxy)-acetic acid and Rinkresin

The following compounds were generated according to example 242

MH+ Example Compound name Starting materials (found) 417N-(3-Fluoro-5-{5-[(R)-1-(2- 1-{2-[3-(3-Amino-5-fluoro- 439.1phenoxy-acetyl)-piperidin-2- phenyl)-[1,2,4]oxadiazol-5-yl]-yl]-[1,2,4]oxadiazol-3-yl}- piperidin-1-yl}-2-phenoxy- phenyl)-acetamideethanone and acetyl chloride 418 N-(2-Fluoro-5-{5-[(R)-1-(2-Boc-D-Pipecolic Acid,N-[2- 439.1 phenoxy-acetyl)-piperidin-2-Fluoro-5-(N- yl]-[1,2,4]oxadiazol-3-yl}- hydroxycarbamidoyl)-phenyl]-phenyl)-acetamide acetamide and phenoxyacetyl chloride 419N-(3-{5-[(R)-1-(2-Phenoxy- 1-{2-[5-(3-Amino-phenyl)-2H- 434.5acetyl)-piperidin-2-yl]-1H- [1,2,4]triazol-3-yl]-piperidin-1-[1,2,4]triazol-3-yl}-phenyl)- yl}-2-phenoxy-ethanone and propionamidepropionic acid chloride 420 N-(3-{5-[(R)-1-(2-Phenoxy-1-{2-[5-(3-Amino-phenyl)-2H- 448.6 acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl]-piperidin-1- [1,2,4]triazol-3-yl}-phenyl)-yl}-2-phenoxy-ethanone and isobutyramide isobutyric acid chloride

The following compounds were generated according to example 1

MH+ Example Compound name Starting materials (found) 421N-(4-Fluoro-3-{5-[(R)-1-(2- 2-Hydrazinocarbonyl- 438.5phenoxy-acetyl)-piperidin-2- piperidine-1-carboxylic acidyl]-1H-[1,2,4]triazol-3-yl}- tert-butyl ester, N-(3- phenyl)-acetamideCarbamidoyl-4-fluoro-phenyl)- acetamide and phenoxyacetic acid 422N-(3-Fluoro-5-{5-[(R)-1-(2- 2-Hydrazinocarbonyl- 348.5phenoxy-acetyl)-piperidin-2- piperidine-1-carboxylic acidyl]-1H-[1,2,4]triazol-3-yl}- tert-butyl ester, N-(3- phenyl)-acetamideCarbamimidoyl-5-fluoro- phenyl)-acetamide and phenoxyacetic acid 423N-(2-Fluoro-5-{5-[(R)-1-(2- 2-Hydrazinocarbonyl- 348.5phenoxy-acetyl)-piperidin-2- piperidine-1-carboxylic acidyl]-1H-[1,2,4]triazol-3-yl}- tert-butyl ester, N-(3- phenyl)-acetamideCarbamimidoyl-6-fluoro- phenyl)-acetamide and phenoxyacetic acid

Example 424N-(4-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-pyridin-2-yl)-acetamide

The title compound was generated in analogy to example 242 from1-{2-[5-(2-Amino-pyridin-4-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanoneand acetyl chloride.

MS 421.5 (MH+)

Example 4251-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-azetidin-2-one

75 mg of1-{2-[5-(3-Amino-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanonewere dissolved in MDF and 40 ul DIPEA added. 34 mg of 3-Bromo-propionylchloride were added at 0° C. and the reaction warmed up to rt andstirred for another 30 min. The reaction mixture was heated to 120° C.using microwave heating and the product was isolated via preparativeHPLC.

MS(ISO): 432.5 (MH+)

Example 4261-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-pyrrolidine-2,5-dione

0.1 mmol of1-{2-[5-(3-Amino-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanonewere dissolved in 1 ml DMF and 1 eq of succinic anhydride added. Thereaction was stirred overnight and the intermediate(N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-succinamicacid) isolated via preparative HPLC. The isolated material wasredissolved in DMF and 1 eq of HATU was added. The reaction mixture washeated to 120° C. using microwave heating. The product was isolated viapreparative HPLC.

MS(ISO): 460.5 (MH+)

Example 4272-Phenoxy-1-[(R)-2-(5-pyridazin-4-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-ethanone

Step 1:

(R)-2-(N-Hydroxycarbamidoyl)-piperidine-1-carboxylic acid tert-butylester

3 g of (R)-N-Boc-2-Cyanopiperidine (14 mmol) were treated with 70 mmolof hydrazine hydrochloride and 35 mmol sodium carbonate in a mixture ofethanol/water (7:3) and heated to 50° C. overnight. The solvent wasevaporated and the crude extracted from ethylacetate/water. The organiclayer was dried over sodium sulfate. After evaporation a white solid wasobtained in quantitative yield.

MS(ISO): 244.5 (MH+)

Step 2:

(R)-2-(5-Pyridazin-4-yl-[1,2,4]oxadiazol-3-yl)-piperidine-1-carboxylicacid tert-butyl ester

0.2 mmol of pyridazine-4-carboxylic acid, HATU and Diisopropylethylaminewere dissolved in 1 ml DMF and stirred for 15 min. 0.2 mmol of(R)-2-(N-Hydroxycarbamidoyl)-piperidine-1-carboxylic acid tert-butylester were added. The reaction was heated to 80° C. and stirredovernight. The DMF was evaporated and the crude extracted fromethylacetate/water. The crude product was not further characterized.

Step 3:

(R) 4-(3-Piperidin-2-yl-[1,2,4]oxadiazol-5-yl)-pyridazinetrifluoroacetate

Crude material from step 3 was treated with neat TFA at room temperaturefor 1 h. The solvent was evaporated. The crude product was not furthercharacterized.

Step 4:

2-Phenoxy-1-[(R)-2-(5-pyridazin-4-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-ethanone

Crude material from step 3 was dissolved in 1 ml DMF and 0.1 mmol DIPEA.Either 0.1 mmol phenoxyacetyl chloride were added and the reactionstirred at room temperature for 30 min, or the correspondingphenoxyacetic acid derivatives were pre-activated with HATU/DIPEA in DMFfor 10 min and added to the crude material from step 3. The product wasisolated via preparative high performance liquid chromatography (HPLC).

MS(ISO): 366.5 (MH+)

The following compounds were generated in analogy to example 427

MH+ Example Compound name Starting materials (found) 4284-{3-[(R)-1-(2-Phenoxy- (R)-2-(N Hydroxycarbamidoyl)- 389.3acetyl)-piperidin-2-yl]- piperidine-1- [1,2,4]oxadiazol-yl}- carboxylicacid tert-butyl ester, benzonitrile 4-Cyanobenzoic acid andPhenoxyacetyl chloride 429 1-{(R)-2-[5-(3-Amino- (R)-2-(NHydroxycarbamidoyl)- 381.3 pyrazin-2-yl)-[1,2,4]oxadiazol- piperidine-1-3-yl]-piperidin-1-yl}-2- carboxylic acid tert-butyl ester,phenoxy-ethanone 3-Amino-pyrazine-2-carboxylic acid and phenoxyacetylchloride 430 3-{3-[(R)-1-(2-Phenoxy- (R)-2-(N Hydroxycarbamidoyl)- 389.3acetyl)-piperidin-2-yl]- piperidine-1- [1,2,4]oxadiazol-5-yl}-carboxylic acid tert-butyl ester, benzonitrile 3-Cyanobenzoic acid andphenoxyacetyl chloride 431 1-{(R)-2-[5-(2-Hydroxy- (R)-2-(NHydroxycarbamidoyl)- 379.4 pyridin-3-yl)-[1,2,4]oxadiazol- piperidine-1-(M − H+) 3-yl]-piperidin-1-yl}-2- carboxylic acid tert-butyl ester,phenoxy-ethanone 2-Hydroxy-nicotinic and phenoxyacetyl chloride 4321-{(R)-2-[5-(5-Amino- (R)-2-(N Hydroxycarbamidoyl)- 380.3pyridin-3-yl)-[1,2,4]oxadiazol- piperidine-1- 3-yl]-piperidin-1-yl}-2-carboxylic acid tert-butyl ester, phenoxy-ethanone 5-Amino-nicotinicacid and phenoxyacetyl chloride 433 1-{(R)-2-[5-(2-Hydroxy- (R)-2-(NHydroxycarbamidoyl)- 381.2 pyridin-4-yl)-[1,2,4]oxadiazol- piperidine-1-3-yl]-piperidin-1-yl}-2- carboxylic acid tert-butyl ester,phenoxy-ethanone 2-Hydroxy-isonicotinic acid and phenoxyacetyl chloride434 1-{(R)-2-[5-(2-Hydroxy-6- (R)-2-(N Hydroxycarbamidoyl)- 395.2methyl-pyridin-4-yl)- piperidine-1- [1,2,4]oxadiazol-3-yl]- carboxylicacid tert-butyl ester, piperidin-1-yl}-2-phenoxy- 2-Hydroxy-6-methyl-ethanone isonicotinic acid and phenoxyacetyl chloride 4351-{(R)-2-[5-(4-Hydroxy- (R)-2-(N Hydroxycarbamidoyl)- 381.2pyridin-2-yl)-[1,2,4]oxadiazol- piperidine-1- 3-yl]-piperidin-1-yl}-2-carboxylic acid tert-butyl ester, phenoxy-ethanone 4-Hydroxy-pyridine-2-carboxylic acid and phenoxyacetyl chloride 436 1-{(R)-2-[5-(2-Amino-5-(R)-2-(N Hydroxycarbamidoyl)- 415.2 chloro-pyrimidin-4-yl)-piperidine-1- [1,2,4]oxadiazol-3-yl]- carboxylic acid tert-butyl ester,piperidin-1-yl}-2-phenoxy- 2-Amino-5-chloro-pyrimidine- ethanone4-carboxylic acid and phenoxyacetyl chloride 437 2-Phenoxy-1-[(R)-2-(5-(R)-2-(N Hydroxycarbamidoyl)- 366.2 pyrazin-2-yl-[1,2,4]oxadiazol-piperidine-1- 3-yl)-piperidin-1-yl]-ethanone carboxylic acid tert-butylester, Pyrazine-2-carboxylic acid and phenoxyacetyl chloride 4382-Phenoxy-1-{(R)-2-[5-(4- (R)-2-(N Hydroxycarbamidoyl)- 431.2[1,2,4]triazol-1-yl-phenyl)- piperidine-1- [1,2,4]oxadiazol-3-yl]-carboxylic acid tert-butyl ester, piperidin-1-yl}-ethanone4-[1,2,4]Triazol-1-yl-benzoic acid and phenoxyacetyl chloride 4392-Phenoxy-1-{(R)-2-[5-(4- (R)-2-(N Hydroxycarbamidoyl)- 432.2tetrazol-1-yl-phenyl)- piperidine-1- [1,2,4]oxadiazol-3-yl]- carboxylicacid tert-butyl ester, piperidin-1-yl}-ethanone 4-Tetrazol-1-yl-benzoicacid and phenoxyacetyl chloride 440 1-{(R)-2-[5-(1H- (R)-2-(NHydroxycarbamidoyl)- 404.2 Benzoimidazol-4-yl)- piperidine-1-[1,2,4]oxadiazol-3-yl]- carboxylic acid tert-butyl ester,piperidin-1-yl}-2-phenoxy- 1H-Benzoimidazole-4- ethanone carboxylic acidand phenoxyacetyl chloride 441 1-{(R)-2-[5-(4-Acetyl-phenyl)- (R)-2-(NHydroxycarbamidoyl)- 406.2 [1,2,4]oxadiazol-3-yl]- piperidine-1-piperidin-1-yl}-2-phenoxy- carboxylic acid tert-butyl ester, ethanone4-Acetyl-benzoic acid and phenoxyacetyl chloride 4421-{(R)-2-[5-(6-Hydroxy- (R)-2-(N Hydroxycarbamidoyl)- 381.2pyridin-2-yl)-[1,2,4]oxadiazol- piperidine-1- 3-yl]-piperidin-1-yl}-2-carboxylic acid tert-butyl ester, phenoxy-ethanone 6-Hydroxy-pyridine-2-carboxylic acid and phenoxyacetyl chloride 443 1-{(R)-2-[5-(5-Methyl-(R)-2-(N Hydroxycarbamidoyl)- 380.2 pyrazin-2-yl)-[1,2,4]oxadiazol-piperidine-1- 3-yl]-piperidin-1-yl}-2- carboxylic acid tert-butyl ester,phenoxy-ethanone 5-Methyl-pyrazine-2-carboxylic acid and phenoxyacetylchloride 444 2-Phenoxy-1-[(R)-2-(5- (R)-2-(N Hydroxycarbamidoyl)- 416.2quinoxalin-2-yl- piperidine-1- [1,2,4]oxadiazol-3-yl)- carboxylic acidtert-butyl ester, piperidin-1-yl]-ethanone Quinoxaline-2-carboxylic acidand phenoxyacetyl chloride 445 1-{(R)-2-[5-(3- (R)-2-(NHydroxycarbamidoyl)- 442.2 Methanesulfonyl-phenyl)- piperidine-1-[1,2,4]oxadiazol-3-yl]- carboxylic acid tert-butyl ester,piperidin-1-yl}-2-phenoxy- 3-Methanesulfonyl-benzoic acid ethanone andphenoxyacetyl chloride 446 1-{(R)-2-[5-(6-Chloro- (R)-2-(NHydroxycarbamidoyl)- 399.1 pyridin-3-yl)-[1,2,4]oxadiazol- piperidine-1-3-yl]-piperidin-1-yl}-2- carboxylic acid tert-butyl ester,phenoxy-ethanone 6-Chloro-nicotinic acid and phenoxyacetyl chloride 4471-[(R)-2-(5-Benzothiazol-6-yl- (R)-2-(N Hydroxycarbamidoyl)- 421.2[1,2,4]oxadiazol-3-yl)- piperidine-1- piperidin-1-yl]-2-phenoxy-carboxylic acid tert-butyl ester, ethanone Benzothiazole-6-carboxylicacid and phenoxyacetyl chloride 448 2-Phenoxy-1-{(R)-2-[5-(2,4,5-(R)-2-(N Hydroxycarbamidoyl)- 418.2 trifluoro-phenyl)- piperidine-1-[1,2,4]oxadiazol-3-yl]- carboxylic acid tert-butyl ester,piperidin-1-yl}-ethanone 2,4,5-Trifluoro-benzoic acid and phenoxyacetylchloride 449 2-Phenoxy-1-{(R)-2-[5-(6- (R)-2-(N Hydroxycarbamidoyl)-433.2 trifluoromethyl-pyridin-3-yl)- piperidine-1-[1,2,4]oxadiazol-3-yl]- carboxylic acid tert-butyl ester,piperidin-1-yl}-ethanone 6-Trifluoromethyl-nicotinic acid andphenoxyacetyl chloride 450 1-[(R)-2-(5- (R)-2-(N Hydroxycarbamidoyl)-422.2 Benzo[1,2,3]thiadiazol-5-yl- piperidine-1- [1,2,4]oxadiazol-3-yl)-carboxylic acid tert-butyl ester, piperidin-1-yl]-2-phenoxy-Benzo[1,2,3]thiadiazole-5- ethanone carboxylic acid and phenoxyacetylchloride 451 1-[(R)-2-(5- (R)-2-(N Hydroxycarbamidoyl)- 416.2[1,8]Naphthyridin-2-yl- piperidine-1- [1,2,4]oxadiazol-3-yl)- carboxylicacid tert-butyl ester, piperidin-1-yl]-2-phenoxy- [1,8]Naphthyridine-2-ethanone carboxylic acid and phenoxyacetyl chloride 452 1-[(R)-2-(5-(R)-2-N Hydroxycarbamidoyl)- 416.2 [1,6]Naphthyridin-2-yl- piperidine-1-[1,2,4]oxadiazol-3-yl)- carboxylic acid tert-butyl ester,piperidin-1-yl]-2-phenoxy- [1,6]Naphthyridine-2- ethanone carboxylicacid and phenoxyacetyl chloride 453 1-[(R)-2-(5-Cinnolin-4-yl- (R)-2-(NHydroxycarbamidoyl)- 416.2 [1,2,4]oxadiazol-3-yl)- piperidine-1-piperidin-1-yl]-2-phenoxy- carboxylic acid tert-butyl ester, ethanoneCinnoline-4-carboxylic acid and phenoxyacetyl chloride 4541-{(R)-2-[5-(1H-Benzotriazol- (R)-2-(N Hydroxycarbamidoyl)- 405.25-yl)-[1,2,4]oxadiazol-3-yl]- piperidine-1- piperidin-1-yl}-2-phenoxy-carboxylic acid tert-butyl ester, ethanone 1H-Benzotriazole-5-carboxylicacid and phenoxyacetyl chloride 455 1-{(R)-2-[5-(1H- (R)-2-(NHydroxycarbamidoyl)- 404.2 Benzoimidazol-5-yl)- piperidine-1-[1,2,4]oxadiazol-3-yl]- carboxylic acid tert-butyl ester,piperidin-1-yl}-2-phenoxy- 1H-Benzoimidazole-5- ethanone carboxylic acidand phenoxyacetyl chloride 456 1-{(R)-2-[5-(3,6-Dichloro- (R)-2-(NHydroxycarbamidoyl)- 435.2 pyridazin-4-yl)- piperidine-1-[1,2,4]oxadiazol-3-yl]- carboxylic acid tert-butyl ester,piperidin-1-yl}-2-phenoxy- 3,6-Dichloro-pyridazine-4- ethanonecarboxylic acid and phenoxyacetyl chloride 457 6-{3-[(R)-1-(2-Phenoxy-(R)-2-(N Hydroxycarbamidoyl)- 435.2 acetyl)-piperidin-2-yl]-piperidine-1- [1,2,4]oxadiazol-5-yl}-4H- carboxylic acid tert-butylester, benzo[1,4]oxazin-3-one 3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid and phenoxyacetyl chloride 4581-{(R)-2-[5-(3H-Imidazo[4,5- (R)-2-(N Hydroxycarbamidoyl)- 405.1b]pyridin-6-yl)- piperidine-1- [1,2,4]oxadiazol-3-yl]- carboxylic acidtert-butyl ester, piperidin-1-yl}-2-phenoxy-3H-Imidazo[4,5-b]pyridine-6- ethanone carboxylic acid and phenoxyacetylchloride 459 N-(4-{3-[(R)-1-(2-Phenoxy- (R)-2-(N Hydroxycarbamidoyl)-422.2 acetyl)-piperidin-2-yl]- piperidine-1-[1,2,4]oxadiazol-5-yl}-pyridin- carboxylic acid tert-butyl ester2-yl)-acetamide 2-Acetylamino-isonicotinic acid and phenoxyacetic acid460 1-{(R)-2-[5-(6-Chloro-3- (R)-2-(N Hydroxycarbamidoyl)- 416.1hydroxy-pyridazin-4-yl)- piperidine-1- [1,2,4]oxadiazol-3-yl]-carboxylic acid tert-butyl ester, piperidin-1-yl}-2-phenoxy-6-Chloro-3-hydroxy- ethanone pyridazine-4-carboxylic acid andphenoxyacetyl chloride 461 6-{3-[(R)-1-(2-Phenoxy- (R)-2-(NHydroxycarbamidoyl)- 448.1 acetyl)-piperidin-2-yl]- piperidine-1-[1,2,4]oxadiazol-5-yl}-1,4- carboxylic acid tert-butyl ester,dihydro-quinoxaline-2,3-dione 2,3-Dioxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxylic acid and phenoxyacetyl chloride 4621-{(R)-2-[5-(6-Hydroxy- (R)-2-(N Hydroxycarbamidoyl)- 381.1pyridin-3-yl)-[1,2,4]oxadiazol- piperidine-1- 3-yl]-piperidin-1-yl}-2-carboxylic acid tert-butyl ester, phenoxy-ethanone 6-Hydroxy-nicotinicacid and phenoxyacetyl chloride 463 7-{3-[(R)-1-(2-Phenoxy- (R)-2-(NHydroxycarbamidoyl)- 434.2 acetyl)-piperidin-2-yl]- piperidine-1-[1,2,4]oxadiazol-5-yl}-3,4- carboxylic acid tert-butyl ester,dihydro-1H-quinoxalin-2-one 3-Oxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxylic acid and phenoxyacetic acid 4641-{(R)-2-[5-(6-Amino- (R)-2-(N Hydroxycarbamidoyl)- 380.2pyridin-2-yl)-[1,2,4]oxadiazol- piperidine-1- 3-yl]-piperidin-1-yl}-2-carboxylic acid tert-butyl ester, phenoxy-ethanone6-Amino-pyridine-2-carboxylic acid and phenoxyacetic acid 4656-{3-[(R)-1-(2-Phenoxy- (R)-2-(N Hydroxycarbamidoyl)- 390.1acetyl)-piperidin-2-yl]- piperidine-1- [1,2,4]oxadiazol-5-yl}-carboxylic acid tert-butyl ester, nicotinonitrile5-Cyano-pyridine-2-carboxylic acid and phenoxyacetic acid 4665-{3-[(R)-1-(2-Phenoxy- (R)-2-(N Hydroxycarbamidoyl)- 390.1acetyl)-piperidin-2-yl]- piperidine-1- [1,2,4]oxadiazol-5-yl}-carboxylic acid tert-butyl ester, pyridine-2-carbonitrile6-Cyano-nicotinic acid and phenoxyacetic acid 4674-{3-[(R)-1-(2-Phenoxy- (R)-2-(N Hydroxycarbamidoyl)- 420.2acetyl)-piperidin-2-yl]- piperidine-1- [1,2,4]oxadiazol-5-yl}-1,2-carboxylic acid tert-butyl ester, dihydro-indazol-3-one3-Oxo-2,3-dihydro-1H- indazole-4-carboxylic acid and phenoxyacetic acid468 1-{(R)-2-[5-(2-Amino- (R)-2-(N Hydroxycarbamidoyl)- 380.1pyridin-4-yl)-[1,2,4]oxadiazol- piperidine-1- 3-yl]-piperidin-1-yl}-2-carboxylic acid tert-butyl ester, phenoxy-ethanone 2-Amino-isonicotinicacid and phenoxyacetic acid 469 1-{(R)-2-[5-(6-Hydroxy- (R)-2-(NHydroxycarbamidoyl)- 382.1 pyrimidin-4-yl)- piperidine-1-[1,2,4]oxadiazol-3-yl]- carboxylic acid tert-butyl ester,piperidin-1-yl}-2-phenoxy- 6-Hydroxy-pyrimidine-4- ethanone carboxylicacid and phenoxyacetic acid 470 4-(3-{3-[(R)-1-(2-Phenoxy- (R)-2-(NHydroxycarbamidoyl)- 447.2 acetyl)-piperidin-2-yl]- piperidine-1-[1,2,4]oxadiazol-5-yl}-phenyl)- carboxylic acid tert-butyl ester,2,4-dihydro-[1,2,4]triazol-3- 3-(5-Oxo-1,5-dihydro- one[1,2,4]triazol-4-yl)-benzoic acid and phenoxyacetic acid 4711-(3-{3-[(R)-1-(2-Phenoxy- (R)-2-(N Hydroxycarbamidoyl)- 462.2acetyl)-piperidin-2-yl]- piperidine-1- [1,2,4]oxadiazol-5-yl}-phenyl)-carboxylic acid tert-butyl ester, imidazolidine-2,4-dione3-(2,4-Dioxo-imidazolidin-1- yl)-benzoic acid and phenoxyacetic acid 4721-((R)-2-{5-[3-(1,1-Dioxo- (R)-2-(N Hydroxycarbamidoyl)- 483.21$$6-isothiazolidin-2-yl)- piperidine-1- phenyl]-[1,2,4]oxadiazol-3-yl}-carboxylic acid tert-butyl ester, piperidin-1-yl)-2-phenoxy-3-(1,1-Dioxo-1$$6- ethanone isothiazolidin-2-yl)-benzoic acid andphenoxyacetic acid 473 1-(3-{3-[(R)-1-(2-Phenoxy- (R)-2-(NHydroxycarbamidoyl)- 447.2 acetyl)-piperidin-2-yl]- piperidine-1-[1,2,4]oxadiazol-5-yl}-phenyl)- carboxylic acid tert-butyl ester,pyrrolidin-2-one 3-(2-Oxo-pyrrolidin-1-yl)- benzoic acid andphenoxyacetic acid 474 1-(3-{3-[(R)-1-(2-Phenoxy- (R)-2-(NHydroxycarbamidoyl)- 446.2 acetyl)-piperidin-2-yl]- piperidine-1-[1,2,4]oxadiazol-5-yl}-phenyl)- carboxylic acid tert-butyl ester,1,3-dihydro-imidazol-2-one 3-(2-Oxo-2,3-dihydro- imidazol-1-yl)-benzoicacid and phenoxyacetic acid 475 3-(3-{3-[(R)-1-(2-Phenoxy- (R)-2-(NHydroxycarbamidoyl)- 462.2 acetyl)-piperidin-2-yl]- piperidine-1-[1,2,4]oxadiazol-5-yl}-phenyl)- carboxylic acid tert-butyl ester,imidazolidine-2,4-dione 3-(2,5-Dioxo-imidazolidin-1- yl)-benzoic acidand phenoxyacetic acid 476 1-{(R)-2-[5-(1-Methyl-1H- (R)-2-(NHydroxycarbamidoyl)- 368.2 pyrazol-3-yl)-[1,2,4]oxadiazol- piperidine-1-3-yl]-piperidin-1-yl}-2- carboxylic acid tert-butyl ester,phenoxy-ethanone 1-Methyl-1H-pyrazole-3- carboxylic acid andphenoxyacetic acid 477 2-Phenoxy-1-{(R)-2-[5-(1H- (R)-2-(NHydroxycarbamidoyl)- 354.1 pyrazol-3-yl)-[1,2,4]oxadiazol- piperidine-1-3-yl]-piperidin-1-yl}-ethanone carboxylic acid tert-butyl ester,1H-Pyrazole-3-carboxylic acid and phenoxyacetic acid 4781-{(R)-2-[5-(5-Methyl- (R)-2-(N Hydroxycarbamidoyl)- 369.1isoxazol-3-yl)- piperidine-1- [1,2,4]oxadiazol-3-yl]- carboxylic acidtert-butyl ester, piperidin-1-yl}-2-phenoxy-5-Methyl-isoxazole-3-carboxylic ethanone acid and phenoxyacetic acid 4791-{(R)-2-[5-(2,5-Dimethyl- (R)-2-(N Hydroxycarbamidoyl)- 382.22H-pyrazol-3-yl)- piperidine-1- [1,2,4]oxadiazol-3-yl]- carboxylic acidtert-butyl ester, piperidin-1-yl}-2-phenoxy- 2,5-Dimethyl-2H-pyrazole-3-ethanone carboxylic acid and phenoxyacetic acid 4801-{(R)-2-[5-(5-Methyl-2H- (R)-2-(N Hydroxycarbamidoyl)- 368.2pyrazol-3-yl)-[1,2,4]oxadiazol- piperidine-1- 3-yl]-piperidin-1-yl}-2-carboxylic acid tert-butyl ester, phenoxy-ethanone5-Methyl-2H-pyrazole-3- carboxylic acid and phenoxyacetic acid 4811-{(R)-2-[5-(3-Methyl- (R)-2-(N Hydroxycarbamidoyl)- 369.1isoxazol-5-yl)- piperidine-1- [1,2,4]oxadiazol-3-yl]- carboxylic acidtert-butyl ester, piperidin-1-yl}-2-phenoxy-3-Methyl-isoxazole-5-carboxylic ethanone acid and phenoxyacetic acid

The following intermediate compounds were prepared in analogy to example256

Example Intermediate name Starting materials 482N-Hydroxy-2-imidazol-1-yl- 2-Imidazol-1-yl-isonicotinonitrileisonicotinamidine and hydroxylamine 483 N-Hydroxy-4-(3H-imidazol-4-yl)-4-(3H-Imidazol-4-yl)-benzonitrile benzamidine and hydroxylamine 484N-Hydroxy-4-(2-methyl-imidazol-1- 4-(2-Methyl-imidazol-1-yl)-yl)-benzamidine benzonitrile and hydroxylamine 485N-Hydroxy-2-pyrazol-1-yl- 2-Pyrazol-1-yl-isonicotinonitrileisonicotinamidine and hydroxylamine 4865-(N-Hydroxycarbamidoyl)-nicotinic 5-Cyano-nicotinic acid ethyl esteracid ethyl ester and hydroxylamine 487 N-Hydroxy-4-piperidin-1-yl-4-Piperidin-1-yl-benzonitrile and benzamidine hydroxylamine 488N-Hydroxy-4-morpholin-1-yl- 4-Morpholin-1-yl-benzonitrile andbenzamidine hydroxylamine 489 N-Hydroxy-6-imidazol-1-yl-6-Imidazol-1-yl-nicotinonitrile and nicotinamidine hydroxylamine 490N-[3-(N-Hydroxycarbamidoyl)- N-(3-Cyano-phenyl)-acetamidephenyl]-acetamide and hydroxylamine 491 4-(N-Hydroxycarbamidoyl)-benzoicN-(3-Cyano-phenyl)-4-Cyano- acid benzyl ester benzoic acid benzyl esterand hydroxylamine 492 5-(N-Hydroxycarbamidoyl)-pyridine-5-Cyano-pyridine-2-carboxylic acid 2-carboxylic acid methyl ester methylester and hydroxylamine 493 2-Fluoro-4-(N-hydroxycarbamidoyl)-4-Cyano-2-fluoro-benzoic acid benzoic acid ethyl ester ethyl ester andhydroxylamine 494 4-(N-Hydroxycarbamidoyl)-benzoic 4-Cyano-benzoic acidmethyl ester acid methyl ester and hydroxylamine 495[3-(N-Hydroxycarbamidoyl)- (3-Cyano-phenoxy)-acetic acid phenoxy]-aceticacid methyl ester methyl ester and hydroxylamine 496N-Hydroxy-2-methyl-1H- 2-Methyl-1H-benzoimidazole-5-benzoimidazole-5-carboxamidine carbonitrile and hydroxylamine 4972-Amino-N-hydroxy- 2-Amino-isonicotinonitrile and isonicotinamidinehydroxylamine 498 3,N-Dihydroxy-benzamidine 3-Hydroxy-benzonitrile andhydroxylamine 499 4,N-Dihydroxy-benzamidine 4-Hydroxy-benzonitrile andhydroxylamine 500 4-(N-Hydroxycarbamimidoyl)- 4-Cyano-phenylboronic acidand benzoic acid hydroxylamine 501 N-Hydroxy-furan-2-carboxamidineFuran-2-carbonitrile and hydroxylamine 502 N-Hydroxy-4-methyl-4-Methyl-[1,2,3]thiadiazole-5- [1,2,3]thiadiazole-5-carboxamidinecarbonitrile and hydroxylamine 503 N-Hydroxy-2,5-dimethyl-2H-2,5-Dimethyl-2H-pyrazole-3- pyrazole-3-carboxamidine carbonitrile andhydroxylamine 504 N-Hydroxy-1H-pyrazole-4- 1H-Pyrazole-4-carbonitrileand carboxamidine hydroxylamine 505 N-Hydroxy-5-methyl-isoxazole-3-5-Methyl-isoxazole-3-carbonitrile carboxamidine and hydroxylamine 506N-Hydroxy-1H-pyrazole-3- 1H-Pyrazole-3-carbonitrile and carboxamidinehydroxylamine 507 N-Hydroxy-2,4-dioxo-1,2,3,4-2,4-Dioxo-1,2,3,4-tetrahydro- tetrahydro-pyrimidine-5-pyrimidine-5-carbonitrile and carboxamidine hydroxylamine 5086-Amino-N-hydroxy-nicotinamidine 6-Amino-nicotinonitrile andhydroxylamine 509 N-Hydroxy-imidazo[1,2-a]pyridine-Imidazo[1,2-a]pyridine-6- 6-carboxamidine carbonitrile and hydroxylamine510 N-[4-Fluoro-3-(N- N-(3-Cyano-4-fluoro-phenyl)-hydroxycarbamimidoyl)-phenyl]- acetamide and hydroxylamine acetamide 511N-[5-Fluoro-3-(N- N-(3-Cyano-5-fluoro-phenyl)-hydroxycarbamimidoyl)-phenyl]- acetamide and hydroxylamine acetamide 512N-[6-Fluoro-3-(N- N-(3-Cyano-6-fluoro-phenyl)-hydroxycarbamimidoyl)-phenyl]- acetamide and hydroxylamine acetamide 513N-Hydroxy-3-oxo-3,4-dihydro-2H- 3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxamidine benzo[1,4]oxazine-6-carbonitrile andhydroxylamine 514 N-Hydroxy-2-oxo-1,4-dihydro-2H- 2-Oxo-1,4-dihydro-2H-benzo[d][1,3]oxazine-6- benzo[d][1,3]oxazine-6- carboxamidinecarbonitrile and hydroxylamine 515 N-Hydroxy-2-oxo-1,2,3,4-tetrahydro-2-Oxo-1,2,3,4-tetrahydro- quinazoline-7-carboxamidinequinazoline-7-carbonitrile and hydroxylamine 5163-(1,1-Dioxo-1□6-isothiazolidin-2- 3-(1,1-Dioxo-1□6-isothiazolidin-2-yl)-N-hydroxy-benzamidine yl)-benzonitrile and hydroxylamine 517N-Hydroxy-3-(2-oxo-pyrrolidin-1- 3-(2-Oxo-pyrrolidin-1-yl)-yl)-benzamidine benzonitrile and hydroxylamine 5183-(2,4-Dioxo-imidazolidin-1-yl)-N- 3-(2,4-Dioxo-imidazolidin-1-yl)-hydroxy-benzamidine benzonitrile and hydroxylamine 519N-Hydroxy-3-(5-oxo-1,5-dihydro- 3-(5-Oxo-1,5-dihydro-[1,2,4]triazol-4-yl)-benzamidine [1,2,4]triazol-4-yl)-benzonitrile andhydroxylamine

The following compounds were generated according to example 312

Example Intermediate name Starting materials 520N-Amino-2-Oxo-2,3-dihydro-1H- 2-Oxo-2,3-dihydro-1H-indole-5-indole-5-carboxamidine hydrochloride carbonitrile and hydrazine 521N-Amino-1H-Indazole-5- 1H-Indazole-5-carbonitrile and carboxamidinehydrochloride hydrazine 522 N-Amino-1H-Indole-5-1H-Indole-5-carbonitrile and carboxamidine hydrochloride hydrazine 523N-Amino-1H-Benzotriazole-5- 1H-Benzotriazole-5-carbonitrilecarboxamidine hydrochloride and hydrazine 524N-Amino-2-Oxo-2,3-dihydro-1H- 2-Oxo-2,3-dihydro-1H-benzoimidazole-5-carboxamidine benzoimidazole-5-carbonitrile andhydrochloride hydrazine 525 N-Amino-N-Hydroxy-2-methyl-1H-2-Methyl-1H-benzoimidazole-5- benzoimidazole-5-carboxamidinecarbonitrile and hydrazine hydrochloride 526 N-Amino-2-Amino-2-Amino-isonicotinonitrile and isonicotinamidine hydrochloride hydrazine527 N-Amino-3-(5-Oxo-4,5-dihydro- 3-(5-Oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl)-benzamidine [1,3,4]oxadiazol-2-yl)-benzonitrilehydrochloride and hydrazine 528 N-Amino-3-[1,3,4]Oxadiazol-2-yl-3-[1,3,4]Oxadiazol-2-yl- benzamidine hydrochloride benzonitrile andhydrazine 529 N-Amino-3-Carbamidoyl- 3-Cyano-phenylboronic acid andphenylboronic acid hydrochloride hydrazine 530N-Amino-2-fluoro-benzamidine 2-Fluorobenzonitrile and hydrazinehydrochloride and hydrazine 531 N-Amino-6-Amino-nicotinamidine6-Amino-nicotinonitrile and hydrochloride hydrazine 532N-Amino-4-Carbamimidoyl-benzoic 4-Cyano-benzoic acid methyl ester acidmethyl ester hydrochloride and hydrazine 533N-Amino-4-Fluoro-benzamidine 4-Fluoro-benzonitrile and hydrochloridehydrazine 534 N-Amino-3-Fluoro-benzamidine 3-Fluoro-benzonitrile andhydrochloride hydrazine

Example 535 N-(5-Cyano-2-fluoro-phenyl)-acetamide

10 mmol of 3-Amino-4-fluoro-benzonitrile were dissolved in 30 ml THF.1.5 eq of DIPEA were added and the reaction mixture cooled to 0° C. 1.2eq of acetylchloride were added dropwise, the reaction warmed up to rtand stirred for additional 30 min. The solvent was evaporated and theproduct isolated via extraction from ethylacetate and saturated NaHCO₃solution.

MS(ISO): 179.2 (MH+)

Example 536 N-(3-Cyano-5-fluoro-phenyl)-acetamide

The title compound was prepared in analogy to example 535 from3-Amino-5-Fluoro-benzonitril. MS(ISO): 179.2 (MH+)

Example 537 N-(3-Cyano-4-fluoro-phenyl)-acetamide

The title compound was prepared in analogy to example 535 from5-Amino-2-Fluoro-benzonitril. MS(ISO): 179.2 (MH+)

Example 538 3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonitrile

24 mmol of 4-Hydroxy-3-nitrobenzonitrile were dissolved in DMF. 1.1 eqof Cs2CO3 were added and the reaction stirred at rt for 15 min. 1.5 eqof ethylbromo acetate were added and the reaction mixture heated to 50°C. for 2 h. The intermediate was isolated via extraction fromethylacetate/water. The organic layer was separated and dried overNa2SO4. After evaporation the resulting solid was redissolved in MeOHand sat. NH4Cl (1:1). 8 g of Zn powder were added and the suspensionstirred at rt for 2 h. The solid was filtered off and the organic layerevaporated. Ethylacetate was added and the organic layer washed withsat. NaHCO3. The organic layer was separated again, dried over Na2SO4and reduced resulting in a light brown solid. MS(ISO): 175.2 (MH+)

Example 539 2-Oxo-1,4-dihydro-2H-benzo[d][1,3]oxazine-6-carbonitrile

20 mmol of 4-Amino-3-hydroxymethyl-benzonitrile were dissolved in THF.1.2 eq. of DIPEA were added and the reaction cooled to 0° C. 3.5 eq ofethyl chloroformate were added dropwise and the reaction warmed to rtand stirred for another 15 min. The crude material was extracted formetyhlacetate and sat. NaHCO3. After separation, and drying of theorganic layer the solvent was evaporated and the crude taken up intoluene. 2.5 ml of DBU were added and the reaction mixture refluxed for4 h. The organic layer was extracted with water and the organic layerseparated and reduced resulting in a yellow oil. Crude material was notfurther characterized.

Example 540 2-Oxo-1,2,3,4-tetrahydro-quinazoline-7-carbonitrile

24 mmol of 2-Nitro-4-chloro-benzylamine hydrochloride were dissolved inTHF. 2.2 eq of DIPEA were added and the reaction mixture cooled to 0° C.3.5 eq. of ethyl chloroforamte were added dropwise and the reactionstirred for 15 min. After extraction from ethylacetate/sat. NaHCO3 andevaporation of the organic layer a light brown solid resulted. This wastaken up in MeOH/sat. NH4Cl (1:1). 6 g of Zn was added and thesuspension stirred at rt for 4 h. The solid was filtered off, themethanol reduced and the product isolated via extraction withethylacetate. After evaporation a light yellow solid resulted. MS(ISO):174.2 (MH+)

Example 541 3-(5-Oxo-1,5-dihydro-[1,2,4]triazol-4-yl)-benzonitrile

g of 3-Aminobenzonitril were dissolved in 20 ml MeOH. 1.8 ml oftrimethyl orthoformate, hydrazinecarboxylic acid methyl ester and cat.para-toluenesulfonic acid were added. The reaction mixture was heated to65° C. for 3 h. The suspension was cooled to rt and 9 ml of NaOMesolution were added and the reaction mixture stirred at rt for 2 h.Water was added and the pH adjusted to 1 using aq. HCl (25%). Theresulting suspension was filtered off and dried under vacuum. MS(ISO):187.2 (MH+)

Example 542 3-(2,4-Dioxo-imidazolidin-1-yl)-benzonitrile

g of 3-Aminobenzonitril were dissolved in 60 ml Dioxan and 0.8 ml ofChloro-acetyl isocyanate added. The reaction mixture was stirred at rtfor 2 h. 2.5 ml of DBU were added and the reaction mixture stirred at rtfor 40 h. The product was extracted with DCM. MS(ISO): 202.2 (MH+)

Example 543 3-(1,1-Dioxo-1λ6-isothiazolidin-2-yl)-benzonitrile

1 g of 3-Aminobenzonitril were dissolved in 10 ml DCM and 2.2 ml ofDIPEA. 1.3 ml of 3-Chloro-propane-1-sulfonyl chloride were added and thereaction mixture stirred at rt overnight. The organic layer wasevaporated, the crude taken up in DMF and 1.5 ml DBU added. The reactionmixture was stirred at rt overnight. DCM was added and the organic phasewashed with water. The organic layer was separated, dried over Na2SO4and evaporated. MS(ISO): 232.2 (MH+)

Example 544 3-(2-Oxo-pyrrolidin-1-yl)-benzonitrile

g of 3-Aminobenzonitril were dissolved in 20 ml DMF and 4.4 ml of DIPEA.The reaction mixture was cooled to 0° C. and 2 ml of 4-chloro-butyrylchloride added. The reaction mixture was stirred at rt for 1 h. 5 ml ofDBU were added and the reaction mixture stirred at rt overnight. DCM wasadded and the organic phase washed with 1N HCL and water. The organiclayer was separated, dried over Na2SO4 and evaporated. MS(ISO): 187.2(MH+)

Example 545 6-Chloro-3-hydroxy-pyridazine-4-carboxylic acid

2 mmol of 3,6-Dichloropyridazine-4-carboxylic acid are treated with 8 mlof aqueous 2N NaOH and refluxed for 1 h. The reaction mixture wasacidified to pH=1. The resulting white solid was filtered off and driedunder vacuum. MS(ISO): 173.2 (M−H+)

Example 546 3-(5-Oxo-1,5-dihydro-[1,2,4]triazol-4-yl)-benzoic acid

13 mmol of methyl-3-aminobenzoate were dissolved in 20 ml MeOH. 12 mmolof trimethylorthoformiate, 12 mmol methyl hydrazinocarboxylate and 50 mgof p-toluenesulfonic acid were added. The suspension was heated for 48 hto 65° C. 37 mmol of sodium methanolate were added and stirred foradditional 2 h. The organic layer was reduced and water was added. Thesolution was acidified to pH=1 and the resulting solid filtered off toresult in 5.7 mmol of product. MS(ISO): 204.2 (M−H+)

Example 547 3-(2,4-Dioxo-imidazolidin-1-yl)-benzoic acid

12 mmol of ethyl-3-aminobenzoate were dissolved in 120 ml Dioxan. 1 eqof chloroacetyl isocyanate were added. The reaction mixture was stirredat rt for 1 h and then heated to 120° C. for an additional 2 h. Thereaction was cooled to rt, 2 eq of DBU added and again stirred at rtovernight. The solvent was evaporated and the crude extracted from DCM.The crude material was dissolved in 20 ml MeOH and 4 ml of 4N NaOH wereadded. The reaction mixture was stirred at rt for 20 h. Afterevaporation of the organic layer the aqueous phase was acidified to pH=1and the resulting white solid was filtered off and dried under vacuum.MS(ISO): 219.2 (M−H+)

Example 548 3-(1,1-Dioxo-1λ6-[1,2,5]thiadiazolidin-2-yl)-benzoic acid

13 mmol of methyl-3-aminobenzoate were dissolved in 20 ml DCM and 3 mlof TEA added. 1.6 ml of 3-chloropropanesulfonyl chloride were addedslowly under argon atmosphere. The reaction mixture was stirred at rtovernight and washed with 1N HCl. The organic layer was separated, driedover Na2SO4 and reduced under vacuum. The resulting crude was taken upin 16 ml DMF and 2.4 ml of DBU added. The reaction mixture was stirredat rt for 2 h and washed with 1N HCl. The crude material was dissolvedin 20 ml MeOH and 4 ml of 2N NaOH were added. The reaction mixture wasstirred at rt for 72 h and acidified with HCl to pH=1. The resultingwhite solid was filtered off and dried under vacuum. MS(ISO): 241.3(M−H+)

Example 549 3-(2-Oxo-2,3-dihydro-imidazol-1-yl)-benzoic acid

12 mmol of ethyl-3-aminobenzoate were dissolved in 20 ml DCM and 2 ml ofTEA added. The reaction mixture was cooled to ° C. and 1.5 ml Diphosgenwere added slowly. The reaction mixture was warmed to rt and stirred foran additional 1 h under argon atmosphere. The reaction mixture waspoured on ice and the organic layer separated, dried over Na2SO4 andreduced under vacuum. The crude material was taken up in 30 ml DCM and1.3 ml of aminoacetaldehyde dimethylacetal were added. The reactionmixture was stirred for 3 h at rt. The organic layer was washed withsat. NaHCO3, separated and dried over Na2SO4. After evaporation of thesolvent the resulting crude material was purified via Kieselgelchromatography. 200 mg of the product were dissolved in 5 ml MeOH and 2ml of 2N NaOH added. The reaction mixture was stirred at rt for 2 h,acidified with HCl to pH=1 and the resulting white solid filtered off.MS(ISO): 203.2 (M−H+)

Example 550 3-(2,5-Dioxo-imidazolidin-1-yl)-benzoic acid

13 mmol of methyl-3-aminobenzoate were dissolved in 20 ml DCM and 1.7 mlof ethyl isocyanatoacetate added. The reaction mixture was stirred at rtfor 1 h. The solvent was evaporated and the resulting crude taken up in50 ml acetone. 50 ml of aq. HCl (25%) were added and heated to refluxfor 8 h. After evaporation of the organic layer the resulting solid wasfiltered off, washed with water and dried under vacuum. MS(ISO): 219.2(M−H+)

Example 551 3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxamidine

8.7 mmol ofN-Hydroxy-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxamidine weredissolved in 25 ml acetic acid. 5 eq. of ammonium formiate and 0.05 eq.of Pd/C (10%) were added and the reaction mixture heated to refluxovernight. The reaction mixture was concentrated, cooled to 0° C. andthe pH adjusted to 8 using aq. NaOH (28%). The resulting solid wasfiltered off and washed with water. MS(ISO): 192.2 (M−H+)

The following intermediate compounds were generated in analogy toexample 551

Example Intermediate name Starting material 552Imidazo[1,2-a]pyridine-6-carboxamidine N-Hydroxy-imidazo[1,2-a]pyridine-6-carboxamidine 553 1H-Benzoimidazole-5-carboxamidineN-Hydroxy-1H-benzoimidazole-5- carboxamidine 554 NicotinamidineN-Hydroxy-nicotinamidine 555 3,5-Dimethyl-isoxazole-4-N-Hydroxy-3,5-dimethyl- carboxamidine isoxazole-4-carboxamidine 556Thiophene-2-carboxamidine N-Hydroxy-thiophene-2- carboxamidine 556Pyrimidine-2-carboxamidine N-Hydroxy-pyrimidine-2- carboxamidine 5574-Methyl-oxazole-5-carboxamidine N-Hydroxy-4-methyl-oxazole-5-carboxamidine 558 Pyrazine-2-carboxamidine N-Hydroxy-pyrazine-2-carboxamidine 559 2-Methyl-isonicotinamidine N-Hydroxy-2-methyl-isonicotinamidine 560 2-Oxo-1,4-dihydro-2H-N-Hydroxy-2-oxo-1,4-dihydro-2H- benzo[d][1,3]oxazine-6-benzo[d][1,3]oxazine-6- carboxamidine carboxamidine 5612-Oxo-1,2,3,4-tetrahydro- N-Hydroxy-2-oxo-1,2,3,4-quinazoline-6-carboxamidine tetrahydro-quinazoline-6- carboxamidine 5623-(2,4-Dioxo-imidazolidin-1-yl)- 3-(2,4-Dioxo-imidazolidin-1-yl)-benzamidine N-hydroxy-benzamidine 563 N-(3-Carbamidoyl-4-fluoro-phenyl)-N-[4-Fluoro-3-(N- acetamide hydroxycarbamidoyl)-phenyl]- acetamide 564N-(3-Carbamidoyl-5-fluoro-phenyl)- N-[5-Fluoro-3-(N- acetamidehydroxycarbamidoyl)-phenyl]- acetamide 565N-(3-Carbamidoyl-6-fluoro-phenyl)- N-[6-Fluoro-3-(N- acetamidehydroxycarbamidoyl)-phenyl]- acetamide

Example A

Film coated tablets containing the following ingredients can bemanufactured in a conventional manner:

Ingredients Per tablet Kernel: Compound of formula (I) 10.0 mg 200.0 mgMicrocrystalline cellulose 23.5 mg 43.5 mg Lactose hydrous 60.0 mg 70.0mg Povidone K30 12.5 mg 15.0 mg Sodium starch glycolate 12.5 mg 17.0 mgMagnesium stearate 1.5 mg 4.5 mg (Kernel Weight) 120.0 mg 350.0 mg FilmCoat: Hydroxypropyl methyl cellulose 3.5 mg 7.0 mg Polyethylene glycol6000 0.8 mg 1.6 mg Talc 1.3 mg 2.6 mg Iron oxyde (yellow) 0.8 mg 1.6 mgTitan dioxide 0.8 mg 1.6 mg

The active ingredient is sieved and mixed with microcristallinecellulose and the mixture is granulated with a solution ofpolyvinylpyrrolidon in water. The granulate is mixed with sodium starchglycolate and magesiumstearate and compressed to yield kernels of 120 or350 mg respectively. The kernels are lacquered with an aqueoussolution/suspension of the above mentioned film coat.

Example B

Capsules containing the following ingredients can be manufactured in aconventional manner:

Ingredients Per capsule Compound of formula (I) 25.0 mg Lactose 150.0 mgMaize starch 20.0 mg Talc 5.0 mg

The components are sieved and mixed and filled into capsules of size 2.

Example C

Injection solutions can have the following composition:

Compound of formula (I) 3.0 mg Polyethylene Glycol 400 150.0 mg AceticAcid q.s. ad pH 5.0 Water for injection solutions ad 1.0 ml

The active ingredient is dissolved in a mixture of Polyethylene Glycol400 and water for injection (part). The pH is adjusted to 5.0 by AceticAcid. The volume is adjusted to 1.0 ml by addition of the residualamount of water. The solution is filtered, filled into vials using anappropriate overage and sterilized.

Example D

Soft gelatin capsules containing the following ingredients can bemanufactured in a conventional manner:

Capsule contents Compound of formula (I) 5.0 mg Yellow wax 8.0 mgHydrogenated Soya bean oil 8.0 mg Partially hydrogenated plant oils 34.0mg Soya bean oil 110.0 mg Weight of capsule contents 165.0 mg Gelatincapsule Gelatin 75.0 mg Glycerol 85% 32.0 mg Karion 83 8.0 mg (drymatter) Titanium dioxide 0.4 mg Iron oxide yellow 1.1 mg

The active ingredient is dissolved in a warm melting of the otheringredients and the mixture is filled into soft gelatin capsules ofappropriate size. The filled soft gelatin capsules are treated accordingto the usual procedures.

Example E

Sachets containing the following ingredients can be manufactured in aconventional manner:

Compound of formula (I) 50.0 mg Lactose, fine powder 1015.0 mgMicrocristalline cellulose (AVICEL PH 102) 1400.0 mg Sodiumcarboxymethyl cellulose 14.0 mg Polyvinylpyrrolidon K 30 10.0 mgMagnesium stearate 10.0 mg Flavoring additives 1.0 mg

The active ingredient is mixed with lactose, microcristalline celluloseand sodium carboxymethyl cellulose and granulated with a mixture ofpolyvinylpyrrolidon in water. The granulate is mixed withmagnesiumstearate and the flavouring additives and filled into sachets.

It is to be understood that the invention is not limited to theparticular embodiments of the invention described above, as variationsof the particular embodiments may be made and still fall within thescope of the appended claims.

1. A compound of formula (I):

wherein: X is C(R⁸R⁹); R¹ is phenyl optionally substituted with 1 to 3substituents selected from the group consisting of halogen, hydroxy,lower-alkyl, hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-alkoxy andCN; R² is hydrogen or lower-alkyl; R³ and R⁴ independently from eachother are hydrogen, halogen, lower-alkyl or lower-alkoxy, or R³ and R⁴together are ═O to form a carbonyl group together with the carbon atomto which they are attached; R⁵ and R⁶ independently from each other arehydrogen, halogen, lower-alkyl or lower-alkoxy, or R⁵ and R⁶ togetherare ═O to form a carbonyl group together with the carbon atom to whichthey are attached; R⁷ is an oxadiazolyl or triazolyl, which oxadiazolylor triazolyl is substituted with R¹¹ and optionally substituted withR¹²; R⁸ and R⁹ independently from each other are hydrogen, halogen,hydroxy, lower-alkyl, lower-alkoxy; or R⁸ and R⁹ are bound together and—R⁸—R⁹— is —(CH₂)₂₋₇— to form a ring together with the carbon atom towhich they are attached; R¹¹ is aryl or a heteroaryl selected from thegroup consisting of pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one,oxadiazolyl, indazolyl, 1,3-dihydro-benzimidazol-2-one,1,3-dihydro-indol-2-one, benztriazolyl, imidazopyridinyl,triazolepyridinyl, tetrazolepyridinyl, benzimidazolyl,2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl,pyrazolyl, isoxazolyl, pyrimidine-2,4-dione, benzooxazin-3-one,1,4-dihydro-benzooxazin-2-one, indolyl, thiophenyl, oxazolyl,benzooxazin-2-one, 3,4-dihydro-quinazolin-2-one, pyridazinyl,quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl,cinnolinyl, 1,4-dihydro-quinoxaline-2,3-dione and1,2-dihydro-indazol-3-one, which aryl or heteroaryl is optionallysubstituted with 1 to 3 substituents selected from the group consistingof lower-alkyl, hydroxy, B(OH)₂, carboxy-lower-alkoxy,carbamoyl-lower-alkoxy, cyano, hydroxy-lower-alkyl, fluoro-lower-alkyl,lower-alkoxy, halogen, S(O₂)R¹³, C(O)R¹⁴, NO₂, NR¹⁵R¹⁶, imidazolyl,pyrazolyl, tetrazolyl, pyrrolyl, phenyl-lower-alkoxy,[1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, whichimidazolyl is optionally substituted with lower-alkyl, and whichphenyl-lower-alkoxy is optionally substituted with hydroxy, halogen,lower-alkyl, lower-alkoxy or fluoro-lower-alkyl, and which pyrazolyl isoptionally substituted with lower-alkyl, and which isoxazolyl isoptionally substituted with lower-alkyl; R¹² is hydrogen or lower-alkyl;R¹³ is lower-alkyl, NR¹⁷R¹⁸ or fluoro-lower-alkyl; R¹⁴ is OH, NR¹⁹R²⁰,lower-alkoxy, lower-alkenyl-oxy or lower-alkyl; R¹⁵ and R¹⁶independently from each other are hydrogen, lower-alkyl,lower-alkyl-carbonyl, lower-alkyl-SO₂, lower-alkenyl-oxy-carbonyl,NH₂-carbonyl, lower-alkyl-NH-carbonyl, (lower-alkyl)₂N-carbonyl orphenyl-lower-alkyl, which phenyl-lower-alkyl is optionally substitutedwith hydroxy, halogen, lower-alkyl, lower-alkoxy or fluoro-lower-alkyl;or NR¹⁵R¹⁶ is a heterocyclyl selected from the group consisting ofmorpholinyl, thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, piperidinyl,piperidin-2-one, piperazin-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl,piperazinyl, pyrrolidinyl, 1,1-dioxo-isothiazolidinyl, pyrrolidin-2-one,imidazolidine-2,4-dione, 2,4-dihydro[1,2,4]triazol-3-one,pyrrolidine-2,5-dione, azetidin-2-one and 1,3-dihydro-imidazol-2-one,which heterocyclyl is optionally substituted with hydroxy-lower-alkyl orlower-alkyl-carbonyl; R¹⁷ and R¹⁸ independently from each other arehydrogen, lower-alkyl, hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl; orNR¹⁷R¹⁸ is morpholinyl; R¹⁹ and R²⁰ independently from each other arehydrogen, lower-alkyl, cycloalkyl, hydroxy-lower-alkyl,lower-alkoxy-lower-alkyl, (lower-alkyl)₂N-lower-alkyl,pyridinyl-lower-alkyl or cyano-lower-alkyl; or NR¹⁹R²⁰ is a heterocyclylselected from the group consisting of morpholinyl, pyrrolidinyl,8-oxa-3-aza-bicyclo[3.2.1]octyl, piperidinyl, piperazinyl,piperazin-2-one, thiazolidinyl, thiomorpholinyl,1,3,8-triaza-spiro[4,5]decane-2,4-dione andspiro(1-phtalan)-piperidine-4-yl, which heterocyclyl is optionallysubstituted with hydroxy, lower-alkyl-S(O₂), lower-alkyl,lower-alkyl-carbonyl, carboxy, carbamoyl, lower-alkoxy-carbonyl, cyano,phenyl, pyridinyl or lower-alkoxy; and pharmaceutically acceptable saltsand esters thereof.
 2. The compound according to claim 1, wherein X isC(R⁸R⁹); R¹ is phenyl optionally substituted with 1 to 3 substituentsselected from the group consisting of halogen, hydroxy, lower-alkyl,hydroxy-lower-alkyl, fluoro-lower-alkyl, lower-alkoxy and CN; R² ishydrogen or lower-alkyl; R³ and R⁴ independently from each other arehydrogen, halogen, lower-alkyl or lower-alkoxy, or R³ and R⁴ togetherare ═O to form a carbonyl group together with the carbon atom to whichthey are attached; R⁵ and R⁶ independently from each other are hydrogen,halogen, lower-alkyl or lower-alkoxy, or R⁵ and R⁶ together are ═O toform a carbonyl group together with the carbon atom to which they areattached; R⁷ is an oxadiazolyl or triazolyl, which oxadiazolyl ortriazolyl is substituted with R¹¹ and optionally substituted with R¹²;R⁸ and R⁹ independently from each other are hydrogen, halogen, hydroxy,lower-alkyl, lower-alkoxy; or R⁸ and R⁹ are bound together and —R⁸—R⁹—is —(CH₂)₂₋₇— to form a ring together with the carbon atom to which theyare attached; R¹¹ is aryl or a heteroaryl selected from the groupconsisting of pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one,oxadiazolyl, indazolyl, 1,3-dihydro-benzimidazol-2-one,1,3-dihydro-indol-2-one, benztriazolyl, imidazopyridinyl,triazolepyridinyl, tetrazolepyridinyl and benzimidazolyl, which aryl orheteroaryl is optionally substituted with 1 to 3 substituents selectedfrom the group consisting of lower-alkyl, hydroxy-lower-alkyl,fluoro-lower-alkyl, lower-alkoxy, halogen, S(O₂)R¹³, C(O)R¹⁴, NO₂,NR¹⁵R¹⁶, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, andphenyl-lower-alkoxy, which imidazolyl is optionally substituted withlower-alkyl and which phenyl-lower-alkoxy is optionally substituted withhydroxy, halogen, lower-alkyl, lower-alkoxy or fluoro-lower-alkyl; R¹²is hydrogen or lower-alkyl; R¹³ is lower-alkyl, NR¹⁷R¹⁸ orfluoro-lower-alkyl; R¹⁴ is OH, NR¹⁹R²⁰, lower-alkoxy orlower-alkenyl-oxy; R¹⁵ and R¹⁶ independently from each other arehydrogen, lower-alkyl, lower-alkyl-carbonyl, lower-alkyl-SO₂,lower-alkenyl-oxy-carbonyl, NH₂-carbonyl, lower-alkyl-NH-carbonyl,(lower-alkyl)₂N-carbonyl or phenyl-lower-alkyl, which phenyl-lower-alkylis optionally substituted with hydroxy, halogen, lower-alkyl,lower-alkoxy or fluoro-lower-alkyl; or NR¹⁵R¹⁶ is a heterocyclylselected from the group consisting of morpholinyl, thiomorpholinyl,1,1-dioxo-thiomorpholinyl, piperidinyl, piperidin-2-one,piperazin-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl andpyrrolidinyl, which heterocyclyl is optionally substituted withhydroxy-lower-alkyl or lower-alkyl-carbonyl; R¹⁷ and R¹⁸ independentlyfrom each other are hydrogen, lower-alkyl, hydroxy-lower-alkyl,lower-alkoxy-lower-alkyl; or NR¹⁷R¹⁸ is morpholinyl; R¹⁹ and R²⁰independently from each other are hydrogen, lower-alkyl, cycloalkyl,hydroxy-lower-alkyl or lower-alkoxy-lower-alkyl; or NR¹⁹R²⁰ is aheterocyclyl selected from the group consisting of morpholinyl,pyrrolidinyl and 8-oxa-3-aza-bicyclo[3.2.1]octyl, which heterocyclyl isoptionally substituted with hydroxy or lower-alkyl-S(O₂); andpharmaceutically acceptable salts and esters thereof.
 3. The compoundaccording to claim 1, wherein R¹ is phenyl optionally substituted withhalogen, hydroxy, hydroxy-lower-alkyl or CN.
 4. The compound accordingto claim 1, wherein R¹ is phenyl.
 5. The compound according to claim 1,wherein R² is hydrogen.
 6. The compound according to claim 1, wherein R³is hydrogen.
 7. The compound according to claim 1, wherein R⁴ ishydrogen.
 8. The compound according to claim 1, wherein R⁵ is hydrogen.9. The compound according to claim 1, wherein R⁶ is hydrogen.
 10. Thecompound according to claim 1, wherein R⁷ is

wherein R¹¹ and R¹² are as defined in claim
 1. 11. The compoundaccording to claim 1, wherein R⁷ is

wherein R¹¹ and R¹² are as defined in claim
 1. 12. The compoundaccording to claim 1, wherein R⁷ is

wherein R¹¹ is as defined in claim
 1. 13. The compound according toclaim 1, wherein R⁸ is hydrogen.
 14. The compound according to claim 1,wherein R⁹ is hydrogen.
 15. The compound according to claim 1, whereinR¹¹ is heteroaryl selected from the group consisting of pyridinyl,pyrazinyl, pyridinyl-2-one, indazolyl, 1,3-dihydro-benzimidazol-2-one,1,3-dihydro-indol-2-one, benztriazolyl and benzimidazolyl, which phenylor heteroaryl is optionally substituted with 1 to 2 substituentsselected from the group consisting of lower-alkyl, hydroxy-lower-alkyl,fluoro-lower-alkyl, lower-alkoxy, halogen, S(O₂)R¹³, C(O)R¹⁴, NO₂,NR¹⁵R¹⁶, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, andphenyl-lower-alkoxy, which imidazolyl is optionally substituted withlower-alkyl, wherein R¹³, R¹⁴, R¹⁵ and R¹⁶ are as defined in claim 1.16. The compound according to claim 1, wherein R¹¹ is phenyl or aheteroaryl selected from the group consisting of pyridinyl,pyridinyl-2-one, indazolyl, 1,3-dihydro-benzimidazol-2-one,1,3-dihydro-indol-2-one, benztriazolyl and benzimidazolyl, which phenylor heteroaryl is optionally substituted with 1 to 2 substituentsselected from the group consisting of fluoro-lower-alkyl, halogen,C(O)R¹⁴ and NR¹⁵R¹⁶, wherein R¹⁴, R¹⁵ and R¹⁶ are as defined in claim 1.17. The compound according to claim 1, wherein R¹¹ is 1H-Indazol-5-yl,1H-Indazol-6-yl, 1,3-dihydro-indol-2-one-6-yl,1,3-dihydro-benzoimidazol-2-one-5-yl, 1,3-dihydro-indol-2-one-5-yl,1H-Benzotriazol-5-yl, 1H-Benzoimidazol-5-yl, 1H-pyridin-2-one-4-yl,4-Fluoro-phenyl, 3-trifluoromethyl-phenyl, 1H-Benzoimidazol-5-yl,3-benzamide, 5-nicotinamide, 3-(N-acetamide)-phenyl or3-(N-methanesulfonamide)-phenyl.
 18. The compound according to claim 1,wherein R¹¹ is phenyl or a heteroaryl selected from the group consistingof 2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl,thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidine-2,4-dione,benzooxazin-3-one, 1,4-dihydro-benzooxazin-2-one, indolyl, thiophenyl,oxazolyl, benzooxazin-2-one, 3,4-dihydro-quinazolin-2-one, pyridazinyl,quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl,cinnolinyl, 1,4-dihydro-quinoxaline-2,3-dione and1,2-dihydro-indazol-3-one, which phenyl or heteroaryl is optionallysubstituted with 1 to 3 substituents selected from the group consistingof hydroxy, B(OH)₂, carboxy-lower-alkoxy, carbamoyl-lower-alkoxy, cyano,[1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, whichpyrazolyl is optionally substituted with lower-alkyl, and whichisoxazolyl is optionally substituted with lower-alkyl.
 19. The compoundaccording to claim 1, wherein R¹¹ is phenyl or a heteroaryl selectedfrom the group consisting of pyridinyl, 1,3-dihydro-indol-2-one,1H-benzimidazolyl, 3H-pyrimidin-4-one, 1H-pyrazolyl, isoxazolyl and4H-benzo[1,4]oxazin-3-one, which phenyl or heteroaryl is optionallysubstituted with 1 to 3 substituents selected from the group consistingof lower-alkyl, hydroxy, halogen and NR¹⁵R¹⁶, wherein R¹⁴ and R¹⁵ are asdefined in claim
 1. 20. The compound according to claim 1, wherein R¹¹is 2-methyl-3H-pyrimidin-4-one, 5-methyl-isoxazol-3-yl, 1H-pyrazol-3-yl,6-amino-pyridin-3-yl, 1,3-dihydro-indol-2-one, 2-amino-pyridin-4-yl,4H-benzo[1,4]oxazin-3-one, 1H-benzimidazol-5-yl,3-(N-acetamide)-4-fluoro-phenyl or 2-hydroxy-pyridin-4-yl.
 21. Thecompound according to claim 1, wherein R¹² is hydrogen.
 22. The compoundaccording to claim 1, wherein R¹³ is lower-alkyl.
 23. The compoundaccording to claim 1, wherein R¹⁴ is NR¹⁹R²⁰, wherein R¹⁹ and R²⁰ are asdefined in claim
 1. 24. The compound according to claim 1, wherein R¹⁴is lower-alkyl.
 25. The compound according to claim 1, wherein R¹⁵ andR¹⁶ independently from each other are hydrogen, lower-alkyl,lower-alkyl-carbonyl, lower-alkyl-SO₂, lower-alkanyl-oxy-carbonyl orlower-alkyl-NH-carbonyl; or NR¹⁵R¹⁶ is a heterocyclyl selected from thegroup consisting of morpholinyl, thiomorpholinyl,1,1-dioxo-thiomorpholinyl, piperidinyl, piperidin-2-one,piperazin-2-one, piperazinyl and pyrrolidinyl, which heterocyclyl isoptionally substituted with hydroxy-lower-alkyl or lower-alkyl-carbonyl.26. The compound according to claim 1, wherein R¹⁵ and R¹⁶ independentlyfrom each other are hydrogen, lower-alkyl-carbonyl or lower-alkyl-SO₂.27. The compound according to claim 1, wherein NR¹⁵R¹⁶ is a heterocyclylselected from the group consisting of 1,1-dioxo-isothiazolidinyl,pyrrolidin-2-one, imidazolidine-2,4-dione,2,4-dihydro[1,2,4]triazol-3-one, pyrrolidine-2,5-dione, azetidin-2-oneand 1,3-dihydro-imidazol-2-one, which heterocyclyl is optionallysubstituted with hydroxy-lower-alkyl or lower-alkyl-carbonyl.
 28. Thecompound according to claim 1, wherein R¹⁷ and R¹⁸ independently fromeach other are hydrogen or lower-alkyl; or NR¹⁷R¹⁸ is morpholinyl. 29.The compound according to claim 1, wherein R¹⁹ and R²⁰ independentlyfrom each other are hydrogen, lower-alkyl, cycloalkyl,hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl; or NR¹⁹R²⁰ is aheterocyclyl selected from the group consisting of morpholinyl orpyrrolidinyl, which heterocyclyl is optionally substituted with hydroxyor lower-alkyl-S(O₂).
 30. The compound according to claim 1, wherein R¹⁹and R²⁰ are hydrogen.
 31. The compound according to claim 1, wherein R¹⁹and R²⁰ independently from each other are (lower-alkyl)₂N-lower-alkyl,pyridinyl-lower-alkyl or cyano-lower-alkyl; or NR¹⁹R²⁰ is a heterocyclylselected from the group consisting of piperidinyl, piperazinyl,piperazin-2-one, thiazolidinyl, thiomorpholinyl,1,3,8-triaza-spiro[4,5]decane-2,4-dione andspiro(1-phtalan)-piperidine-4-yl, which heterocyclyl is optionallysubstituted with hydroxy, lower-alkyl-S(O₂), lower-alkyl,lower-alkyl-carbonyl, carboxy, carbamoyl, lower-alkoxy-carbonyl, cyano,phenyl, pyridinyl or lower-alkoxy.
 32. The compound according to claim1, which are R-isomers and which are characterised by formula (Ia)

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and X are as defined in claim
 1. 33.The compound according to claim 1, selected from the group consisting of(R)-1-{2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-3-(2-{2-[3-(4-Methoxy-phenyl)[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-oxo-ethoxy)benzonitrile,(R)-1-{2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-propan-1-one,(R)-1-{2-[3-(4-Bromo-phenyl)[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-2-(4-Hydroxy-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-2-(4-Chloro-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-2-(4-Hydroxymnethyl-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-2-(3-Chloro-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-2-(4-Fluoro-phenoxy)-1-{2-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-1-{2-[3-(4-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(4-Methane-sulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,(R)-2-(4-Fluoro-phenoxy)-1-[2-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-ethanone,(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoicacid methyl ester,(R)-1-{2-[3-(3-Nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(4-Nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,(R)-2-Phenoxy-1-[2-(3-pyrazin-2-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-ethanone,(R)-1-(2-{3-[4-(Morpholine-4-sulfonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-1-{2-[3-(6-Methoxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(3-Hydroxymethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinicacid allyl ester,(R)-1-{2-[3-(4-Imidazol-1-yl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-N-Methyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,(R)-1-{2-[3-(6-Morpholin-4-yl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-2-Phenoxy-1-{2-[3-(4-trifluoromethanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-2-Phenoxy-1-{2-[3-(4-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-1-{2-[3-(4-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-N-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-2-trifluoromethyl-phenyl)-acetamide,(R)-1-{2-[3-(3-Methanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(4-Methyl-3-nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(4-Methoxy-3-nitro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-N-(2-Hydroxy-ethyl)-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,(R)-N-(2-Methoxy-ethyl)-N-methyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,(R)-N,N-Dimethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,(R)-N,N-Diethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzenesulfonamide,(R)-1-{2-[3-(2-Morpholin-4-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-2-Phenoxy-1-{2-[3-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4′-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-2-Phenoxy-1-{2-[3-(2-thiomorpholin-4-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-1-{2-[3-(2-Diethylamino-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylicacid ethyl ester,(R)-1-(2-{3-[6-(4-Acetyl-piperazin-1-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-1-{2-[3-(2-Imidazol-1-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-piperidin-2-one,(R)-1-(2-{3-[4-(3H-Imidazol-4-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-1-(2-{3-[4-(2-Methyl-imidazol-1-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-2-Phenoxy-1-{2-[3-(2-pyrazol-1-yl-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,(R)-4-(5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridin-2-yl)-piperazin-2-one,(R)-2-Phenoxy-1-(2-{3-[4-(1H-tetrazol-5-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-ethanone,(R)-1-{2-[3-(1H-Indazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(1H-Indazol-6-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(4-Fluoro-3-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-benzoimidazol-2-one,(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,(R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-(2-{3-[6-(1,1-Dioxo-thiomorpholin-4-yl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-N-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridin-2-yl)-acetamide,(R)-1-{2-[3-(6-Benzyloxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinicacid ethyl ester,(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridin-2-one,(R)-2-Phenoxy-1-[2-(5-phenyl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,(R)-1-{2-[5-(4-Methanesulfonyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[5-(3,4-Dimethoxy-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[5-(3,4-Dichloro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxyethanone,(R)-1-{2-[5-(4-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-2-Phenoxy-1-{2-[5-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-ethanone,(R)-1-{2-[5-(4-Methoxy-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[5-(3-Nitro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoicacid methyl ester,(R)-1-{2-[5-(4-Fluoro-3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,3-dihydro-indol-2-one,1-{3-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-morpholin-4-yl}-2-phenoxy-ethanone,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoicacid,(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoicacid,(R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinicacid,(R)-2-Fluoro-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzoicacid,(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylicacid,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylicacid,(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoicacid,(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinicacid,1-(2-{3-[4-(Morpholine-4-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-1-(2-{3-[4-(3-Hydroxy-pyrrolidine-1-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-N,N-Diethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-Methyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N,N-Dimethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-Ethyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-Cyclopropyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-(2-Hydroxy-ethyl)-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-(2-Methoxy-ethyl)-N-methyl-4-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-Methyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N,N-Dimethyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-Ethyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-Cyclopropyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-(2-Hydroxy-ethyl)-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-N-(2-Methoxy-ethyl)-N-methyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-1-(2-{3-[3-(Morpholine-4-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-1-(2-{3-[3-(3-Hydroxy-pyrrolidine-1-carbonyl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-N,N-Diethyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylicacid methylamide,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylicacid dimethylamide,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylicacid ethylamide,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylicacid diethylamide,(R)-1-(2-{3-[2-(Morpholine-4-carbonyl)-pyridin-4-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-1-(2-{3-[2-(3-Methanesulfonyl-pyrrolidine-1-carbonyl)-pyridin-4-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylicacid methylamide,(R)-N-Methyl-3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,(R)-N-Methyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,(R)-N-Ethyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,(R)-N-Diethyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,(R)-N-Diethyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,(R)-N-(2-Hydroxy-ethyl)-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,(R)-N-(2-Methoxy-ethyl)-N-methyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,(R)-N-Cyclopropyl-5-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,(R)-1-(2-{3-[5-(3-Hydroxy-pyrrolidine-1-carbonyl)-pyridin-3-yl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,(R)-4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridine-2-carboxylicacid amide,(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,(R)-1-{2-[3-(3-Amino-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(4-Amino-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[5-(3-Amino-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide,(R)-N-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide,(R)-N-(5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-pyridin-2-yl)-acetamide,(R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,(R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-methanesulfonamide,(R)-N-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-methanesulfonamide,(R)-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-carbamicacid allyl ester,(R)-(4-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-carbamicacid allyl ester,(R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-methanesulfonamide,(R)-1-Ethyl-3-(3-{5-[1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-urea,(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzonitrile,and(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinonitrile,and pharmaceutically acceptable salts and esters thereof.
 34. Thecompound according to claim 1, selected from the group consisting of(R)-1-{2-[3-(1H-Indazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(1H-Indazol-6-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-6-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-benzoimidazol-2-one,(R)-5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydro-indol-2-one,(R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[3-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-1-{2-[5-(4-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,(R)-2-Phenoxy-1-{2-[5-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-ethanone,(R)-3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-benzamide,5-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-nicotinamide,(R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,and(R)-N-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-methanesulfonamide,and pharmaceutically acceptable salts and esters thereof.
 35. Thecompound according to claim 1, selected from the group consisting of1-{(R)-2-[3-(2-Methyl-1H-benzoimidazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[3-(2-Amino-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[3-(3-Hydroxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,4-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridin-2-one,1-{(R)-2-[3-(4-Hydroxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenylboronicacid,4-(2-Oxo-2-{(R)-2-[3-(2-oxo-2,3-dihydro-1H-indol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethoxy)-benzonitrile,4-(2-{(R)-2-[3-(4-Methoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-oxo-ethoxy)-benzonitrile,2-Methyl-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-3H-pyrimidin-4-one,1-[(R)-2-(3-Furan-2-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-2-phenoxy-ethanone,1-[(R)-2-(3-Imidazo[1,2-a]pyridin-2-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-2-phenoxy-ethanone,1-{(R)-2-[3-(4-Methyl-[1,2,3]thiadiazol-5-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[3-(2,5-Dimethyl-2H-pyrazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,2-Phenoxy-1-{(R)-2-[3-(1H-pyrazol-4-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,1-{(R)-2-[3-(5-Methyl-isoxazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,2-Phenoxy-1-{(R)-2-[3-(1H-pyrazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyrimidine-2,4-dione,1-{(R)-2-[3-(6-Amino-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-[(R)-2-(3-Imidazo[1,2-a]pyridin-6-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-2-phenoxy-ethanone,6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-4H-benzo[1,4]oxazin-3-one,6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,4-dihydro-benzo[d][1,3]oxazin-2-one,1-((R)-2-{3-[3-(1,1-Dioxo-1λ6-isothiazolidin-2-yl)-phenyl]-[1,2,4]oxadiazol-5-yl}-piperidin-1-yl)-2-phenoxy-ethanone,1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-pyrrolidin-2-one,1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-imidazolidine-2,4-dione,4-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one,1-(3-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-pyrrolidine-2,5-dione,5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,3-dihydro-indol-2-one,1-{(R)-2-[5-(1H-Indazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(1H-Indol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(3H-Benzotriazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,3-dihydro-benzoimidazol-2-one,1-{(R)-2-[5-(2-Methyl-1H-benzoimidazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(2-Amino-pyridin-4-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,5-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-3H-[1,3,4]oxadiazol-2-one,1-{(R)-2-[5-(3-[1,3,4]Oxadiazol-2-yl-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenylboronicacid,6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-4H-benzo[1,4]oxazin-3-one,1-[(R)-2-(5-Imidazo[1,2-a]pyridin-6-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,1-{(R)-2-[5-(6-Amino-pyridin-3-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(1H-Benzoimidazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,2-Phenoxy-1-[(R)-2-(5-pyridin-3-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,1-{(R)-2-[5-(3,5-Dimethyl-isoxazol-4-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,2-Phenoxy-1-[(R)-2-(5-thiophen-2-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,2-Phenoxy-1-[(R)-2-(5-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,1-{(R)-2-[5-(4-Methyl-oxazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,2-Phenoxy-1-[(R)-2-(5-pyrazin-2-yl-2H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-ethanone,1-{(R)-2-[5-(2-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(3,5-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(2-Methyl-pyridin-4-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(3-Fluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(3,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,4-dihydro-benzo[d][1,3]oxazin-2-one,7-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-3,4-dihydro-1H-quinazolin-2-one,1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-imidazolidine-2,4-dione,(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenoxy)-aceticacid,2-Phenoxy-1-((R)-2-{5-[3-(piperidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-ethanone,1-((R)-2-{5-[3-(Morpholine-4-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,1-((R)-2-{5-[3-(4-Methyl-piperazine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,4-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-piperazin-2-one,N-(2-Methoxy-ethyl)-N-methyl-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,1-((R)-2-{5-[3-(4-Acetyl-piperazine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-piperidine-4-carboxylicacid,1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-piperidine-4-carboxylicacid amide,2-Phenoxy-1-((R)-2-{5-[3-(thiazolidine-3-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-ethanone,N-(2-Dimethylamino-ethyl)-N-methyl-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,2-Phenoxy-1-((R)-2-{5-[3-(thiomorpholine-4-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-ethanone,4-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-piperazine-1-carboxylicacid ethyl ester,N-(2-Hydroxy-ethyl)-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,N-Methyl-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-N-(2-pyridin-2-yl-ethyl)-benzamide,N-(2-Cyano-ethyl)-N-cyclopropyl-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzamide,1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-4-phenyl-piperidine-4-carbonitrile,1-((R)-2-{5-[3-(4-Hydroxy-piperidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,8-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-benzoyl)-1,3,8-triaza-spiro[4.5]decane-2,4-dione,1-(2-{5-[3-(Spiro(1-Phtalan)-piperidine-4-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,2-Phenoxy-1-((R)-2-{5-[3-(3-pyridin-4-yl-pyrrolidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-ethanone,1-((R)-2-{5-[3-(3-Methanesulfonyl-pyrrolidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,1-((R)-2-{5-[3-((S)-3-Ethoxy-pyrrolidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,1-((R)-2-{5-[3-((S)-3-Hydroxy-pyrrolidine-1-carbonyl)-phenyl]-2H-[1,2,4]triazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-nicotinamide,2-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenoxy)-acetamide,N-(3-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide,N-(2-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-phenyl)-acetamide,N-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-propionamide,N-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-isobutyramide,N-(4-Fluoro-3-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,N-(3-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,N-(2-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,N-(4-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-pyridin-2-yl)-acetamide,1-(3-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-azetidin-2-one,1-(3-{5-[1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-pyrrolidine-2,5-dione,2-Phenoxy-1-[(R)-2-(5-pyridazin-4-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-ethanone,4-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-benzonitrile,1-{(R)-2-[5-(3-Amino-pyrazin-2-yi)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-benzonitrile,1-{(R)-2-[5-(2-Hydroxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(5-Amino-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(2-Hydroxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(2-Hydroxy-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(4-Hydroxy-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(2-Amino-5-chloro-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,2-Phenoxy-1-[(R)-2-(5-pyrazin-2-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-ethanone,2-Phenoxy-1-{(R)-2-[5-(4-[1,2,4]triazol-1-yl-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,2-Phenoxy-1-{(R)-2-[5-(4-tetrazol-1-yl-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,1-{(R)-2-[5-(1H-Benzoimidazol-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(4-Acetyl-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(6-Hydroxy-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(5-Methyl-pyrazin-2-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,2-Phenoxy-1-[(R)-2-(5-quinoxalin-2-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-ethanone,1-{(R)-2-[5-(3-Methanesulfonyl-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(6-Chloro-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-[(R)-2-(5-Benzothiazol-6-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,2-Phenoxy-1-{(R)-2-[5-(2,4,5-trifluoro-phenyl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,2-Phenoxy-1-{(R)-2-[5-(6-trifluoromethyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,1-[(R)-2-(5-Benzo[1,2,3]thiadiazol-5-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,1-[(R)-2-(5-[1,8]Naphthyridin-2-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,1-[(R)-2-(5-[1,6]Naphthyridin-2-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,1-[(R)-2-(5-Cinnolin-4-yl-[1,2,4]oxadiazol-3-yl)-piperidin-1-yl]-2-phenoxy-ethanone,1-{(R)-2-[5-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(1H-Benzoimidazol-5-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(3,6-Dichloro-pyridazin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,6-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-4H-benzo[1,4]oxazin-3-one,1-{(R)-2-[5-(3H-Imidazo[4,5-b]pyridin-6-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,N-(4-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-pyridin-2-yl)-acetamide,1-{(R)-2-[5-(6-Chloro-3-hydroxy-pyridazin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,6-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-1,4-dihydro-quinoxaline-2,3-dione,1-{(R)-2-[5-(6-Hydroxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,7-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-3,4-dihydro-1H-quinoxalin-2-one,1-{(R)-2-[5-(6-Amino-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,6-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-nicotinonitrile,5-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-pyridine-2-carbonitrile,4-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-1,2-dihydro-indazol-3-one,1-{(R)-2-[5-(2-Amino-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(6-Hydroxy-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,4-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one,1-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-imidazolidine-2,4-dione,1-((R)-2-{5-[3-(1,1-Dioxo-1λ6-isothiazolidin-2-yl)-phenyl]-[1,2,4]oxadiazol-3-yl}-piperidin-1-yl)-2-phenoxy-ethanone,1-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-pyrrolidin-2-one,1-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-1,3-dihydro-imidazol-2-one,3-(3-{3-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-5-yl}-phenyl)-imidazolidine-2,4-dione,1-{(R)-2-[5-(1-Methyl-1H-pyrazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,2-Phenoxy-1-{(R)-2-[5-(1H-pyrazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-ethanone,1-{(R)-2-[5-(5-Methyl-isoxazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(2,5-Dimethyl-2H-pyrazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(5-Methyl-2H-pyrazol-3-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,and1-{(R)-2-[5-(3-Methyl-isoxazol-5-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,and pharmaceutically acceptable salts and esters thereof.
 36. Thecompound according to claim 1, selected from the group consisting of2-Methyl-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-[1,2,4]oxadiazol-3-yl}-3H-pyrimidin-4-one,1-{(R)-2-[3-(5-Methyl-isoxazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,2-Phenoxy-1-{(R)-2-[3-(1H-pyrazol-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-ethanone,1-{(R)-2-[3-(6-Amino-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-phenoxy-ethanone,5-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-1,3-dihydro-indol-2-one,1-{(R)-2-[5-(2-Amino-pyridin-4-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,6-{5-[(R)-1-(2-Phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-4H-benzo[1,4]oxazin-3-one,1-{(R)-2-[5-(6-Amino-pyridin-3-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,1-{(R)-2-[5-(1H-Benzoimidazol-5-yl)-2H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,N-(2-Fluoro-5-{5-[(R)-1-(2-phenoxy-acetyl)-piperidin-2-yl]-1H-[1,2,4]triazol-3-yl}-phenyl)-acetamide,and1-{(R)-2-[5-(2-Hydroxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-piperidin-1-yl}-2-phenoxy-ethanone,and pharmaceutically acceptable salts and esters thereof.
 37. A processfor the manufacture of a compound according to claim 1, comprising thestep of reacting a compound of formula (II)

with a compound of formula (III)

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, and X are as defined in claim 1 andL is halogen.
 38. A pharmaceutical composition, comprising atherapeutically effective amount of a compound according to claim 1 anda pharmaceutically acceptable carrier and/or adjuvant.